(19)
(11)EP 3 156 503 B1

(12)EUROPEAN PATENT SPECIFICATION

(45)Mention of the grant of the patent:
11.12.2019 Bulletin 2019/50

(21)Application number: 15809520.8

(22)Date of filing:  16.06.2015
(51)International Patent Classification (IPC): 
C12Q 1/6886(2018.01)
(86)International application number:
PCT/JP2015/067267
(87)International publication number:
WO 2015/194535 (23.12.2015 Gazette  2015/51)

(54)

STOMACH CANCER BIOMARKER AND DETECTION METHOD

MAGENKREBS-BIOMARKER UND DETEKTIONSVERFAHREN

BIOMARQUEUR DU CANCER DE L'ESTOMAC ET PROCÉDÉ DE DÉTECTION


(84)Designated Contracting States:
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

(30)Priority: 16.06.2014 JP 2014123224
31.03.2015 JP 2015071485

(43)Date of publication of application:
19.04.2017 Bulletin 2017/16

(60)Divisional application:
19205717.2

(73)Proprietors:
  • Toray Industries, Inc.
    Tokyo 103-8666 (JP)
  • National Cancer Center
    Tokyo 104-0045 (JP)

(72)Inventors:
  • KOZONO, Satoko
    Kamakura-shi Kanagawa 248-8555 (JP)
  • NOBUMASA, Hitoshi
    Kamakura-shi Kanagawa 248-8555 (JP)
  • KONDOU, Satoshi
    Kamakura-shi Kanagawa 248-8555 (JP)
  • SUDO, Hiroko
    Kamakura-shi Kanagawa 248-8555 (JP)
  • KAWAUCHI, Junpei
    Kamakura-shi Kanagawa 248-8555 (JP)
  • OCHIAI, Atsushi
    Kashiwa-shi Chiba 277-8577 (JP)
  • KOJIMA, Motohiro
    Kashiwa-shi Chiba 277-8577 (JP)

(74)Representative: Mewburn Ellis LLP 
City Tower 40 Basinghall Street
London EC2V 5DE
London EC2V 5DE (GB)


(56)References cited: : 
WO-A1-2009/108853
JP-A- 2012 507 300
JP-A- 2013 085 542
WO-A2-2007/081740
JP-A- 2013 085 542
JP-A- 2014 060 993
  
  • M TSUJIURA ET AL: "Circulating microRNAs in plasma of patients with gastric cancers", BRITISH JOURNAL OF CANCER, vol. 102, no. 7, 16 March 2010 (2010-03-16), pages 1174-1179, XP055432146, GB ISSN: 0007-0920, DOI: 10.1038/sj.bjc.6605608
  • RUI LIU ET AL: "A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis", EUROPEAN JOURNAL OF CANCER, ELSEVIER, AMSTERDAM, NL, vol. 47, no. 5, 27 October 2010 (2010-10-27), pages 784-791, XP028182301, ISSN: 0959-8049, DOI: 10.1016/J.EJCA.2010.10.025 [retrieved on 2010-11-01]
  • BO-SHENG LI ET AL: "Plasma microRNAs, miR-223, miR-21 and miR-218, as Novel Potential Biomarkers for Gastric Cancer Detection", PLOS ONE, vol. 7, no. 7, 30 July 2012 (2012-07-30), page e41629, XP055432179, DOI: 10.1371/journal.pone.0041629
  • Genechip: "Data Sheet GeneChip TM miRNA 3.0 Array", , 29 March 2012 (2012-03-29), XP055222758, Retrieved from the Internet: URL:http://www.carrerasresearch.org/genech ip-mirna-3-0-array_38713.pdf [retrieved on 2015-10-21]
  • BERILLO O ET AL: "Binding of intronic miRNAs to the mRNAs of host genes encoding intronic miRNAs and proteins that participate in tumourigenesis", COMPUTERS IN BIOLOGY AND MEDICINE, vol. 43, no. 10, 1 October 2013 (2013-10-01), pages 1374-1381, XP028715750, ISSN: 0010-4825, DOI: 10.1016/J.COMPBIOMED.2013.07.011
  • J. LIU ET AL: "MicroRNA expression profile of gastric cancer stem cells in the MKN-45 cancer cell line", ACTA BIOCHIMICA ET BIOPHYSICA SINICA, vol. 46, no. 2, 2 January 2014 (2014-01-02), pages 92-99, XP055431774, US ISSN: 1672-9145, DOI: 10.1093/abbs/gmt135
  • SATOKO TAKIZAWA: 'DNA Chip 3D- Gene ni yoru Morateki Kesseichu miRNA Kaiseki' BIO CLINICA vol. 29, no. 6, 10 June 2014, pages 78 - 79, XP008185469
  • SATOKO TAKIZAWA: 'DNA Chip 3D- Gene ni yoru FFPE . Kessei Kentai deno Tashu miRNA Doji Kaiseki' BIO CLINICA vol. 28, no. 9, 2013, pages 84 - 85, XP008184667
  • KOJIRO ETO: 'Shokaki Gan to microRNA' RINSHO KAGAKU vol. 43, no. 2, April 2014, pages 99 - 105, XP008185468
  • JI KON RYU ET AL: "Elevated microRNA miR-21 Levels in Pancreatic Cyst Fluid Are Predictive of Mucinous Precursor Lesions of Ductal Adenocarcinoma", PANCREATOLOGY, vol. 11, 1 January 2011 (2011-01-01), pages 343-350, XP055056147, DOI: 10.1159/000329183
  • JULIAN O KIM ET AL: "Non-small Cell Lung Cancer Detection Using MicroRNA Expression Profiling of Bronchoalveolar Lavage Fluid and Sputum", ANTICANCER RESEARCH, vol. 35, no. 4, 1 April 2015 (2015-04-01), pages 1873-1880, XP055593783,
  • SAZANOV A A ET AL: "Plasma and saliva miR-21 expression in colorectal cancer patients", JOURNAL OF APPLIED GENETICS: AN INTERNATIONAL JOURNAL OF GENETICS AND BREEDING, SPRINGER, GERMANY, vol. 58, no. 2, 2 December 2016 (2016-12-02), pages 231-237, XP036212215, ISSN: 1234-1983, DOI: 10.1007/S13353-016-0379-9 [retrieved on 2016-12-02]
  • Annette L Mazzone ET AL: "Circulating and Urinary miR-210 and miR-16 Increase during Cardiac Surgery Using Cardiopulmonary Bypass - A Pilot Study", The journal of extra-corporeal technology, 1 March 2018 (2018-03-01), pages 19-29, XP055593787, United States Retrieved from the Internet: URL:https://www.ncbi.nlm.nih.gov/pmc/artic les/PMC5848080/pdf/ject-50-19.pdf
  
Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).


Description

Technical Field



[0001] The present invention relates to the use of a kit or a device for the detection of stomach cancer, comprising a nucleic acid(s) capable of specifically binding to a particular miRNA(s), which is used for examining the presence or absence of stomach cancer in a subject, and a method for detecting stomach cancer, comprising measuring an expression level(s) of the miRNA(s) using the nucleic acid.

Background Art



[0002] The stomach is a sac-like digestive organ connected to the esophagus. The stomach temporarily stores food from the esophagus and plays a role in the first step of digestion by secreting gastric juice. The stomach is divided into the cardial end located around the inlet leading to the esophagus, the pyloric end located around the outlet leading to the duodenum, and the other site called the gastric corpus (Non-Patent Literature 1). According to the statistics of the number of cancer type-specific incidences and deaths in Japan disclosed by the Center for Cancer Control and Information Services, National Cancer Center, estimated 125,730 individuals in total involving 86,728 males and 39,002 females were affected by stomach cancer in 2010. The number of stomach cancer deaths was a total of 49,129 people involving 32,206 males and 16,923 females in 2012. Thus, stomach cancer was the second leading cause of cancer death in Japan. Also, 22,220 Americans were affected by stomach cancer in 2014, among which 10,990 people would die of stomach cancer (Non-Patent Literature 1).

[0003] The stages of stomach cancer progression are defined in Non-Patent Literature 2 and classified into stages 0, IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV according to tumor size, infiltration, lymph node metastasis, distant metastasis, etc. The 5-year relative survival rate of stomach cancer largely depends on the stages of cancer progression and is reportedly 57 to 71% for stage I, 33 to 46% for stage II, 9 to 20% for stage III, and 4% for stage IV (Non-Patent Literature 1). Thus, the early detection of stomach cancer leads to improvement in the survival rate. Therefore, an approach that enables early detection is strongly desired.

[0004] The treatment of stomach cancer is performed by the combined use of surgical therapy, drug therapy, and radiotherapy. Particularly, in very early stomach cancer under no suspicion of lymph node metastasis, endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is often applicable and the cancer can thus be treated without any burden on patients.

[0005] With the aim of detecting stomach cancer early, Japanese men and women aged 40 or older are recommended to take stomach cancer screening once a year. The efficacy of "gastric X-ray examination" as a method for stomach cancer screening has been shown. When detailed examination is required as a result of X-ray examination, gastroscopy is carried out. Alternatively, diagnostic imaging such as CT, PET, or MRI is also utilized for detecting stomach cancer (Non-Patent Literature 1).

[0006] On the other hand, no blood marker has been established for the screening of stomach cancer. Although the association of protein tumor markers such as CEA and CA19-9 in serum with stomach cancer has been suggested (Non-Patent Literature 3), there is no enough evidence to recommend using these markers for the purpose of screening. Meanwhile, as shown in Patent Literatures 1 to 3, there are reports, albeit at a research stage, on the detection of stomach cancer using the expression levels of microRNAs (miRNAs) or combinations of the expression levels of miRNAs and the expression levels of additional protein markers in biological samples including blood.

[0007] Patent Literature 1 discloses a method for detecting cancers including stomach cancer using hsa-miR-125a-3p in blood.

[0008] Patent Literature 2 discloses a method for detecting stomach cancer using hsa-miR-23a-3p, miR-92-1, and miR-92-2 (miR-92a-1-3p and miR-92a-2-3p) and also using miR-128b (miR-128-2-3p), miR-30c (miR-30c-5p), miR-135-1, miR-135-2 (miR-135a-5p), and miR-149 (miR-149-5p), and other miRNAs in blood or tissues.

[0009] Patent Literature 3 discloses a method for detecting stomach cancer using hsa-miR-451 and 468 (hsa-miR-468-5p) in blood.

Citation List


Patent Literature



[0010] 

Patent Literature 1: International Publication No. WO 2010/062706

Patent Literature 2: JP Patent Publication (Kokai) No. 2014-060993 A (2014)

Patent Literature 3: JP Patent Publication (Kokai) No. 2013-085542 A (2013)


Non-Patent Literature



[0011] 

Non-Patent Literature 1: American Cancer Society, "Stomach Cancer", 2013, p. 3, 6, and 18 to 20, http://www.cancer.org/acs/groups/cid/documents/webcontent/003141-pdf.pdf

Non-Patent Literature 2: Sobin, L. et al, "TNM Classification of Malignant Tumours, the 7th edition, Japanese version", 2010, p. 69 to 73

Non-Patent Literature 3: Kim, H.J. et al., Acta Oncologica, 2009, Vol. 48, p. 385 to 390.


Summary of Invention


Technical Problem



[0012] An object of the present invention is to find a novel tumor marker(s) for stomach cancer and to provide a method that can effectively detect stomach cancer using a nucleic acid(s) capable of specifically binding to the marker(s). Primary tests of stomach cancer include imaging tests such as gastric X-ray examination, which is routinely used in Japan, as well as CT, PET, and MRI (Non-Patent Literature 1). In Japan, however, stomach cancer is still the second leading cause of cancer death. Thus, the imaging tests cannot always work as a deterrent against stomach cancer death.

[0013] For example, CEA and CA19-9 are known as tumor markers for the detection of stomach cancer. In general, as shown in Non-Patent Literature 3, 5 ng/mL for CEA and 37 U/mL for CA19-9 are used as reference values. Although these tumor markers may be helpful in confirming the recurrence of or therapeutic effects on stomach cancer, their expression very rarely elevates in early stomach cancer. Therefore, these markers may not be useful for the purpose of stomach cancer screening. The tumor markers such as CEA and CA19-9 may also elevate for reasons other than those due to stomach cancer. Therefore, these markers alone allegedly fail to determine the presence or absence of stomach cancer. The false diagnosis of other cancers as stomach cancer wastes appropriate therapeutic opportunity or places unnecessary economical and physical burdens on patients due to the application of wrong medicine.

[0014] As described below, there are reports, albeit at a research stage, on the determination of stomach cancer using the expression levels of microRNAs (miRNAs) in biological samples including blood, none of which, however, have yet been brought into practical use.

[0015] Patent Literature 1 discloses a method for detecting cancers including stomach cancer using hsa-miR-125a-3p and other miRNAs in blood. This detection method, however, does not describe specific detection performance such as accuracy, sensitivity, or specificity for determining stomach cancer and is thus industrially less practical.

[0016] Patent Literature 2 discloses a method for detecting stomach cancer using hsa-miR-23a-3p, miR-92-1, and miR-92-2 (miR-92a-1-3p and miR-92a-2-3p) and further using miR-128 (miR-128-2-5p), miR-30c (miR-30c-5p), miR-135-1, miR-135-2 (miR-135a-5p), miR-149 (miR-149-5p), and other miRNAs in blood or tissues.

[0017] Among them, hsa-miR-23a-3p, miR-92-1, and miR-92-2 (miR-92a-1-3p and miR-92a-2-3p) are particularly described as miRNAs for detecting stomach cancer. According to the description therein, these markers in blood, however, were not validated, and specific detection examples were given for miRNAs in tissues. This is not an easy screening test. Therefore, this detection method is industrially less practical.

[0018] As mentioned above, the existing tumor markers exhibit low performance in the detection of stomach cancer, or neither detection methods nor performance is specifically shown as to the markers at a research stage. Therefore, use of these markers might lead to carrying out needless extra examination due to the false detection of healthy subjects as being stomach cancer patients, or might waste therapeutic opportunity because of overlooking stomach cancer patients. In addition, the measurement of dozens to several hundreds of miRNAs increases examination cost and is therefore difficult to use in large-scale screening for medical checkup, etc. Furthermore, the collection of gastric tissues for measuring the tumor markers is highly invasive to patients and is not favorable. Hence, there is a demand for a highly accurate stomach cancer marker that is detectable from blood, which can be collected with limited invasiveness, and is capable of correctly discriminating a stomach cancer patient from a healthy subject. Particularly, screening based on an imaging test, such as gastric X-ray examination, which is currently carried out for the early detection of stomach cancer, presents problems associated with radiation exposure, high cost, etc. Therefore, the provision of a more convenient primary screening test of stomach cancer probably leads to benefits to subjects and the health service.

Solution to Problem



[0019] The present inventors have conducted diligent studies to attain the object and consequently completed the present invention by finding multiple genes usable as markers for the detection of stomach cancer from blood, which can be collected with limited invasiveness, and finding that stomach cancer can be significantly detected by using a nucleic acid(s) capable of specifically binding to any of these markers.

<Summary of Invention>



[0020] Specifically, the present invention has the following features:

In a first aspect the invention provides the use of a stomach cancer marker polynucleotide miR-4257 in an in vitro method of detection or diagnosis of stomach cancer.

In a further aspect, miR-4257 is used together with at least one or more polynucleotide(s) selected from the group consisting of the stomach cancer markers set out in claim 2.

In a further aspect, the use is of a kit comprising a nucleic acid(s) capable of specifically binding to a polynucleotide of stomach cancer marker miR-4257, as set out in claim 3. The polynucleotide may be selected from the group set out in claim 4. The kit may further comprise nucleic acid(s) capable of specifically binding to at least one or more polynucleotides selected from the group consisting of the other stomach cancer markers set out in claim 5 and in some aspects the polynucleotide may be a polynucleotide as set out in claim 6. In a further aspect of the use, the kit may comprise at least two or more nucleic acids capable of specifically binding to at least two or more polynucleotides, respectively, selected from all of the stomach cancer markers set out in claim 5.

In a further aspect, the use is of a device comprising a nucleic acid(s) capable of specifically binding to a polynucleotide of stomach cancer marker miR-4257, as set out in claim 8. The polynucleotide may be selected from the group set out in claim 9. The device may further comprise nucleic acid(s) capable of specifically binding to at least one or more polynucleotides selected from the group consisting of the other stomach cancer markers set out in claim 10 and in some aspects the polynucleotide may be a polynucleotide as set out in claim 11. In some aspects of the use, the device is a device for measurement by a hybridization technique, as set out in claim 12, such as a nucleic acid array technique as set out in claim 13.. In a further aspect of the use, the device may comprise at least two or more nucleic acids capable of specifically binding to at least two or more polynucleotides, respectively, selected from all of the stomach cancer markers set out in claim 10.

In a further aspect the invention provides a method for detecting stomach cancer, comprising measuring an expression level(s) of a target nucleic acid(s) in a sample from a subject using the kit defined in any one of claims 1 to 5 or the device defined in any one of claims 6 to 12, and evaluating in vitro whether or not the subject has stomach cancer using both of the measured expression level(s) and control expression level(s) in a sample from a healthy subject measured in the same way, wherein the target nucleic acid(s) comprise stomach cancer marker polynucleotide miR-4257.

In a further aspect of the method, the target nucleic acid(s) further comprise at least one or more polynucleotide(s) selected from the group consisting of the stomach cancer markers set out in claim 16. In some aspects of the method, the subject is a human, as set out in claim 17. In some aspects of the method the sample is blood, serum, or plasma as set out in claim 18.


<Definition of Terms>



[0021] The terms used herein are defined as follows.

[0022] Abbreviations or terms such as nucleotide, polynucleotide, DNA, and RNA abide by "Guidelines for the preparation of specification which contain nucleotide and/or amino acid sequences" (edited by Japan Patent Office) and common use in the art.

[0023] The term "polynucleotide" used herein refers to a nucleic acid including all of RNA, DNA, and RNA/DNA (chimera). The DNA includes any of cDNA, genomic DNA, and synthetic DNA. The RNA includes any of total RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, non-coding RNA and synthetic RNA. Herein, the "synthetic DNA" and the "synthetic RNA" refer to DNA and RNA artificially prepared using, for example, an automatic nucleic acid synthesizer, on the basis of predetermined nucleotide sequences (which may be any of natural and non-natural sequences). The "non-natural sequence" is intended to be used in a broad sense and includes, for example, a sequence containing substitution, deletion, insertion, and/or addition of one or more nucleotides (i.e., a variant sequence) and a sequence containing one or more modified nucleotides (i.e., a modified sequence), which are different from the natural sequence. Herein, the polynucleotide is used interchangeably with a nucleic acid.

[0024] The term "fragment" used herein is a polynucleotide having a nucleotide sequence having a consecutive portion of a polynucleotide and desirably has a length of 15 or more nucleotides, preferably 17 or more nucleotides, more preferably 19 or more nucleotides.

[0025]  The term "gene" used herein is intended to include not only RNA and double-stranded DNA but also each single-stranded DNA such as a plus strand (or a sense strand) or a complementary strand (or an antisense strand) that constitutes a duplex. The gene is not particularly limited by its length.

[0026] Thus, herein, the "gene" includes any of double-stranded DNA including human genomic DNA, single-stranded DNA (plus strand), single-stranded DNA having a sequence complementary to the plus strand (complementary strand) including cDNA, microRNA (miRNA), and their fragments, and their transcripts, unless otherwise specified. The "gene" includes not only a "gene" represented by a particular nucleotide sequence (or SEQ ID NO) but "nucleic acids" encoding RNAs having biological functions equivalent to RNA encoded by the gene, for example, a congener (i.e., a homolog or an ortholog), a variant (e.g., a genetic polymorph), and a derivative. Specific examples of such a "nucleic acid" encoding a congener, a variant, or a derivative can include a "nucleic acid" having a nucleotide sequence hybridizing under stringent conditions described later to a complementary sequence of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 657 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t. The "gene" is not particularly limited by its functional region and can contain, for example, an expression regulatory region(s), a coding region(s), an exon(s), or an intron(s). The "gene" may be contained in a cell or may exist alone after being released from a cell. Alternatively, the "gene" may be enclosed in a vesicle called exosome.

[0027] The term "exosome" used herein is a vesicle that is delimited by a lipid bilayer and secreted from a cell. The exosome is derived from a multivesicular endosome and may incorporate biomaterials such as a "gene" (e.g., RNA or DNA) or a protein when released into an extracellular environment. The exosome is known to be contained in a body fluid such as blood, serum, plasma, or lymph.

[0028] The term "transcript" used herein refers to an RNA synthesized from the DNA sequence of a gene as a template. RNA polymerase binds to a site called a promoter located upstream of the gene and adds ribonucleotides complementary to the nucleotide sequence of the DNA to the 3' end to synthesize RNA. This RNA contains not only the gene itself but also the whole sequence from a transcription initiation site to the end of a polyA sequence, including an expression regulatory region, a coding region, an exon, or an intron.

[0029] Unless otherwise specified, the term "microRNA (miRNA)" used herein is intended to mean a 15- to 25-nucleotide non-coding RNA that is involved in the suppression of translation of mRNA, and that transcribed as an RNA precursor having a hairpin-like structure, cleaved by a dsRNA-cleaving enzyme which has RNase III cleavage activity, and integrated into a protein complex called RISC. The term "miRNA" used herein includes not only a "miRNA" represented by a particular nucleotide sequence (or SEQ ID NO) but a precursor of the "miRNA" (pre-miRNA or pri-miRNA), and miRNAs having biological functions equivalent thereto, for example, a congener (i.e., a homolog or an ortholog), a variant (e.g., a genetic polymorph), and a derivative. Such a precursor, a congener, a variant, or a derivative can be specifically identified using miRBase Release 20 (http://www.mirbase.org/), and examples thereof can include a "miRNA" having a nucleotide sequence hybridizing under stringent conditions described later to a complementary sequence of any particular nucleotide sequence represented by any of SEQ ID NOs: 1 to 657. The term "miRNA" used herein may be a gene product of a miR gene. Such a gene product includes a mature miRNA (e.g., a 15- to 25-nucleotide or 19- to 25- nucleotide non-coding RNA involved in the suppression of translation of mRNA as described above) or a miRNA precursor (e.g., pre-miRNA or pri-miRNA as described above).

[0030] The term "probe" used herein includes a polynucleotide that is used for specifically detecting RNA resulting from the expression of a gene or a polynucleotide derived from the RNA, and/or a polynucleotide complementary thereto.

[0031] The term "primer" used herein includes a polynucleotide that specifically recognizes and amplifies RNA resulting from the expression of a gene or a polynucleotide derived from the RNA, and/or a polynucleotide complementary thereto.

[0032] In this context, the complementary polynucleotide (complementary strand or reverse strand) means a polynucleotide in a complementary relationship ofA:T (U) and G:C base pairs with the full-length sequence of a polynucleotide consisting of a nucleotide sequence defined by any of SEQ ID NOs: 1 to 657 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, or a partial sequence thereof (here, this full-length or partial sequence is referred to as a plus strand for the sake of convenience). However, such a complementary strand is not limited to a sequence completely complementary to the nucleotide sequence of the target plus strand and may have a complementary relationship to an extent that permits hybridization under stringent conditions to the target plus strand.

[0033] The term "stringent conditions" used herein refers to conditions under which a nucleic acid probe hybridizes to its target sequence to a larger extent (e.g., a measurement value equal to or larger than "(a mean of background measurement values) + (a standard deviation of the background measurement values) × 2") than that for other sequences. The stringent conditions are dependent on a sequence and differ depending on an environment where hybridization is performed. A target sequence that is 100% complementary to the nucleic acid probe can be identified by controlling the stringency of hybridization and/or washing conditions. Specific examples of the "stringent conditions" will be mentioned later.

[0034] The term "Tm value" used herein means a temperature at which the double-stranded moiety of a polynucleotide is denatured into single strands so that the double strands and the single strands exist at a ratio of 1:1.

[0035] The term "variant" used herein means, in the case of a nucleic acid, a natural variant attributed to polymorphism, mutation, or the like; a variant containing the deletion, substitution, addition, or insertion of 1 or 2 or more nucleotides in a nucleotide sequence represented by any of SEQ ID NOs: 1 to 657 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, or a partial sequence thereof; a variant that exhibits percent (%) identity of approximately 90% or higher, approximately 95% or higher, approximately 97% or higher, approximately 98% or higher, approximately 99% or higher to each of these nucleotide sequences or the partial sequences thereof; or a nucleic acid hybridizing under the stringent conditions defined above to a polynucleotide or an oligonucleotide comprising each of these nucleotide sequences or the partial sequences thereof.

[0036]  The term "several" used herein means an integer of approximately 10, 9, 8, 7, 6, 5, 4, 3, or 2.

[0037] The variant used herein can be prepared by use of a well-known technique such as site-directed mutagenesis or PCR-based mutagenesis.

[0038] The term "percent (%) identity" used herein can be determined with or without an introduced gap, using a protein or gene search system based on BLAST or FASTA described above (Zheng Zhang et al., 2000, J. Comput. Biol., Vol. 7, p. 203-214; Altschul, S.F. et al., 1990, Journal of Molecular Biology, Vol. 215, p. 403-410; and Pearson, W.R. et al., 1988, Proc. Natl. Acad. Sci. U. S. A., Vol. 85, p. 2444-2448).

[0039] The term "derivative" used herein is meant to include a modified nucleic acid, for example, a derivative labeled with a fluorophore or the like, a derivative containing a modified nucleotide (e.g., a nucleotide containing a group such as halogen, alkyl such as methyl, alkoxy such as methoxy, thio, or carboxymethyl, and a nucleotide that has undergone base rearrangement, double bond saturation, deamination, replacement of an oxygen molecule with a sulfur atom, etc.), PNA (peptide nucleic acid; Nielsen, P.E. et al., 1991, Science, Vol. 254, p. 1497-500), and LNA (locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., Vol. 39, p. 5401-5404) without any limitation.

[0040] The "nucleic acid" used herein capable of specifically binding to a polynucleotide selected from the stomach cancer marker miRNAs described above is a synthesized or prepared nucleic acid and specifically includes a "nucleic acid probe" or a "primer". The "nucleic acid" is utilized directly or indirectly for detecting the presence or absence of stomach cancer in a subject, for diagnosing the presence or absence of stomach cancer, the severity of stomach cancer, the presence or absence of amelioration or the degree of amelioration of stomach cancer, or the therapeutic sensitivity of stomach cancer, or for screening for a candidate substance useful in the prevention, amelioration, or treatment of stomach cancer. The "nucleic acid" includes a nucleotide, an oligonucleotide, and a polynucleotide capable of specifically recognizing and binding to a transcript represented by any of SEQ ID NOs: 1 to 657 or a synthetic cDNA nucleic acid thereof in vivo, particularly, in a sample such as a body fluid (e.g., blood or urine), in relation to the development of stomach cancer. The nucleotide, the oligonucleotide, and the polynucleotide can be effectively used as probes for detecting the aforementioned gene expressed in vivo, in tissues, in cells, or the like on the basis of the properties described above, or as primers for amplifying the aforementioned gene expressed in vivo.

[0041] The term "detection" used herein is interchangeable with the term "examination", "measurement", "detection", or "decision support". The term "evaluation" used herein is meant to include diagnosis or evaluation support on the basis of examination results or measurement results.

[0042] The term "subject" used herein means a mammal such as a primate including a human and a chimpanzee, a pet animal including a dog and a cat, a livestock animal including cattle, a horse, sheep, and a goat, and a rodent including a mouse and a rat. The term "healthy subject" also means such a mammal without the cancer to be detected.

[0043] The term "P" or "P value" used herein refers to a probability at which a more extreme statistic than that actually calculated from data under null hypothesis is observed in a statistical test. Thus, smaller "P" or "P value" is regarded as being a more significant difference between subjects to be compared.

[0044] The term "sensitivity" used herein means a value of (the number of true positives) / (the number of true positives + the number of false negatives). High sensitivity allows stomach cancer to be detected early, leading to the complete resection of cancer sites and reduction in the rate of recurrence.

[0045] The term "specificity" used herein means a value of (the number of true negatives) / (the number of true negatives + the number of false positives). High specificity prevents needless extra examination for healthy subjects misjudged as being stomach cancer patients, leading to reduction in burden on patients and reduction in medical expense.

[0046]  The term "accuracy" used herein means a value of (the number of true positives + the number of true negatives) / (the total number of cases). The accuracy indicates the ratio of samples that identified correctly in the discriminant results to all samples, and serves as a primary index for evaluating detection performance.

[0047] The "sample" used herein that is subject to determination, detection, or diagnosis refers to a tissue and a biological material in which the expression of the gene of the present invention varies as stomach cancer develops, as stomach cancer progresses, or as therapeutic effects on stomach cancer are exerted. Specifically, the "sample" refers to a gastric tissue, a perigastric vascular channel, lymph node, and organ, an organ suspected of having metastasis, the skin, a body fluid such as blood, urine, saliva, sweat, or tissue exudates, serum or plasma prepared from blood, feces, hair, and the like. The "sample" further refers to a biological sample extracted therefrom, specifically, a gene such as RNA or miRNA.

[0048] The term "hsa-miR-4257 gene" or "hsa-miR-4257" used herein includes the hsa-miR-4257 gene (miRBase Accession No. MIMAT0016878) described in SEQ ID NO: 1, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4257 gene can be obtained by a method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Also, "hsa-mir-4257" (miRBase Accession No. MI0015856, SEQ ID NO: 200) having a hairpin-like structure is known as a precursor of "hsa-miR-4257".

[0049] The term "hsa-miR-6726-5p gene" or "hsa-miR-6726-5p" used herein includes the hsa-miR-6726-5p gene (miRBase Accession No. MIMAT0027353) described in SEQ ID NO: 2, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6726-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6726" (miRBase Accession No. MI0022571, SEQ ID NO: 201) having a hairpin-like structure is known as a precursor of "hsa-miR-6726-5p".

[0050] The term "hsa-miR-1343-3p gene" or "hsa-miR-1343-3p" used herein includes the hsa-miR-1343-3p gene (miRBase Accession No. MIMAT0019776) described in SEQ ID NO: 3, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1343-3p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 202) having a hairpin-like structure is known as a precursor of "hsa-miR-1343-3p".

[0051] The term "hsa-miR-1247-3p gene" or "hsa-miR-1247-3p" used herein includes the hsa-miR-1247-3p gene (miRBase Accession No. MIMAT0022721) described in SEQ ID NO: 4, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1247-3p gene can be obtained by a method described in Morin RD et al., 2008, Genome Res, Vol. 18, p. 610-621. Also, "hsa-mir-1247" (miRBase Accession No. MI0006382, SEQ ID NO: 203) having a hairpin-like structure is known as a precursor of "hsa-miR-1247-3p".

[0052] The term "hsa-miR-6787-5p gene" or "hsa-miR-6787-5p" used herein includes the hsa-miR-6787-5p gene (miRBase Accession No. MIMAT0027474) described in SEQ ID NO: 5, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6787-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6787" (miRBase Accession No. MI0022632, SEQ ID NO: 204) having a hairpin-like structure is known as a precursor of "hsa-miR-6787-5p".

[0053] The term "hsa-miR-6875-5p gene" or "hsa-miR-6875-5p" used herein includes the hsa-miR-6875-5p gene (miRBase Accession No. MIMAT0027650) described in SEQ ID NO: 6, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6875-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6875" (miRBase Accession No. MI0022722, SEQ ID NO: 205) having a hairpin-like structure is known as a precursor of "hsa-miR-6875-5p".

[0054] The term "hsa-miR-1225-3p gene" or "hsa-miR-1225-3p" used herein includes the hsa-miR-1225-3p gene (miRBase Accession No. MIMAT0005573) described in SEQ ID NO: 7, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1225-3p gene can be obtained by a method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336. Also, "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 206) having a hairpin-like structure is known as a precursor of "hsa-miR-1225-3p".

[0055] The term "hsa-miR-8063 gene" or "hsa-miR-8063" used herein includes the hsa-miR-8063 gene (miRBase Accession No. MIMAT0030990) described in SEQ ID NO: 8, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-8063 gene can be obtained by a method described in Wang HJ et al., 2013, Shock, Vol. 39, p. 480-487. Also, "hsa-mir-8063" (miRBase Accession No. MI0025899, SEQ ID NO: 207) having a hairpin-like structure is known as a precursor of "hsa-miR-8063".

[0056] The term "hsa-miR-6781-5p gene" or "hsa-miR-6781-5p" used herein includes the hsa-miR-6781-5p gene (miRBase Accession No. MIMAT0027462) described in SEQ ID NO: 9, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6781-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6781" (miRBase Accession No. MI0022626, SEQ ID NO: 208) having a hairpin-like structure is known as a precursor of "hsa-miR-6781-5p".

[0057] The term "hsa-miR-4746-3p gene" or "hsa-miR-4746-3p" used herein includes the hsa-miR-4746-3p gene (miRBase Accession No. MIMAT0019881) described in SEQ ID NO: 10, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4746-3p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4746" (miRBase Accession No. MI0017385, SEQ ID NO: 209) having a hairpin-like structure is known as a precursor of "hsa-miR-4746-3p".

[0058] The term "hsa-miR-1908-5p gene" or "hsa-miR-1908-5p" used herein includes the hsa-miR-1908-5p gene (miRBase Accession No. MIMAT0007881) described in SEQ ID NO: 11, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1908-5p gene can be obtained by a method described in Bar M et al., 2008, Stem Cells, Vol. 26, p. 2496-2505. Also, "hsa-mir-1908" (miRBase Accession No. MI0008329, SEQ ID NO: 210) having a hairpin-like structure is known as a precursor of "hsa-miR-1908-5p".

[0059] The term "hsa-miR-6756-5p gene" or "hsa-miR-6756-5p" used herein includes the hsa-miR-6756-5p gene (miRBase Accession No. MIMAT0027412) described in SEQ ID NO: 12, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6756-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6756" (miRBase Accession No. MI0022601, SEQ ID NO: 211) having a hairpin-like structure is known as a precursor of "hsa-miR-6756-5p".

[0060] The term "hsa-miR-204-3p gene" or "hsa-miR-204-3p" used herein includes the hsa-miR-204-3p gene (miRBase Accession No. MIMAT0022693) described in SEQ ID NO: 13, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-204-3p gene can be obtained by a method described in Lim LP et al., 2003, Science, Vol. 299, p. 1540. Also, "hsa-mir-204" (miRBase Accession No. MI0000284, SEQ ID NO: 212) having a hairpin-like structure is known as a precursor of "hsa-miR-204-3p".

[0061] The term "hsa-miR-4651 gene" or "hsa-miR-4651" used herein includes the hsa-miR-4651 gene (miRBase Accession No. MIMAT0019715) described in SEQ ID NO: 14, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4651 gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4651" (miRBase Accession No. MI0017279, SEQ ID NO: 213) having a hairpin-like structure is known as a precursor of "hsa-miR-4651".

[0062] The term "hsa-miR-6757-5p gene" or "hsa-miR-6757-5p" used herein includes the hsa-miR-6757-5p gene (miRBase Accession No. MIMAT0027414) described in SEQ ID NO: 15, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6757-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6757" (miRBase Accession No. MI0022602, SEQ ID NO: 214) having a hairpin-like structure is known as a precursor of "hsa-miR-6757-5p".

[0063] The term "hsa-miR-6825-5p gene" or "hsa-miR-6825-5p" used herein includes the hsa-miR-6825-5p gene (miRBase Accession No. MIMAT0027550) described in SEQ ID NO: 16, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6825-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6825" (miRBase Accession No. MI0022670, SEQ ID NO: 215) having a hairpin-like structure is known as a precursor of "hsa-miR-6825-5p".

[0064] The term "hsa-miR-7108-5p gene" or "hsa-miR-7108-5p" used herein includes the hsa-miR-7108-5p gene (miRBase Accession No. MIMAT0028113) described in SEQ ID NO: 17, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-7108-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-7108" (miRBase Accession No. MI0022959, SEQ ID NO: 216) having a hairpin-like structure is known as a precursor of "hsa-miR-7108-5p".

[0065] The term "hsa-miR-4792 gene" or "hsa-miR-4792" used herein includes the hsa-miR-4792 gene (miRBase Accession No. MIMAT0019964) described in SEQ ID NO: 18, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4792 gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4792" (miRBase Accession No. MI0017439, SEQ ID NO: 217) having a hairpin-like structure is known as a precursor of "hsa-miR-4792".

[0066] The term "hsa-miR-7641 gene" or "hsa-miR-7641" used herein includes the hsa-miR-7641 gene (miRBase Accession No. MIMAT0029782) described in SEQ ID NO: 19, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-7641 gene can be obtained by a method described in Yoo JK et al., 2013, Arch Pharm Res, Vol. 36, p. 353-358. Also, "hsa-mir-7641-1 and hsa-mir-7641-2" (miRBase Accession Nos. MI0024975 and MI0024976, SEQ ID NO: 218 and 219) having a hairpin-like structure are known as precursors of "hsa-miR-7641".

[0067] The term "hsa-miR-3188 gene" or "hsa-miR-3188" used herein includes the hsa-miR-3188 gene (miRBase Accession No. MIMAT0015070) described in SEQ ID NO: 20, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3188 gene can be obtained by a method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Also, "hsa-mir-3188" (miRBase Accession No. MI0014232, SEQ ID NO: 220) having a hairpin-like structure is known as a precursor of "hsa-miR-3188".

[0068]  The term "hsa-miR-3131 gene" or "hsa-miR-3131" used herein includes the hsa-miR-3131 gene (miRBase Accession No. MIMAT0014996) described in SEQ ID NO: 21, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3131 gene can be obtained by a method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Also, "hsa-mir-3131" (miRBase Accession No. MI0014151, SEQ ID NO: 221) having a hairpin-like structure is known as a precursor of "hsa-miR-3131".

[0069] The term "hsa-miR-6780b-5p gene" or "hsa-miR-6780b-5p" used herein includes the hsa-miR-6780b-5p gene (miRBase Accession No. MIMAT0027572) described in SEQ ID NO: 22, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6780b-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6780b" (miRBase Accession No. MI0022681, SEQ ID NO: 222) having a hairpin-like structure is known as a precursor of "hsa-miR-6780b-5p".

[0070] The term "hsa-miR-8069 gene" or "hsa-miR-8069" used herein includes the hsa-miR-8069 gene (miRBase Accession No. MIMAT0030996) described in SEQ ID NO: 23, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-8069 gene can be obtained by a method described in Wang HJ et al., 2013, Shock, Vol. 39, p. 480-487. Also, "hsa-mir-8069" (miRBase Accession No. MI0025905, SEQ ID NO: 223) having a hairpin-like structure is known as a precursor of "hsa-miR-8069".

[0071] The term "hsa-miR-6840-3p gene" or "hsa-miR-6840-3p" used herein includes the hsa-miR-6840-3p gene (miRBase Accession No. MIMAT0027583) described in SEQ ID NO: 24, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6840-3p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6840" (miRBase Accession No. MI0022686, SEQ ID NO: 224) having a hairpin-like structure is known as a precursor of "hsa-miR-6840-3p".

[0072] The term "hsa-miR-8072 gene" or "hsa-miR-8072" used herein includes the hsa-miR-8072 gene (miRBase Accession No. MIMAT0030999) described in SEQ ID NO: 25, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-8072 gene can be obtained by a method described in Wang HJ et al., 2013, Shock, Vol. 39, p. 480-487. Also, "hsa-mir-8072" (miRBase Accession No. MI0025908, SEQ ID NO: 225) having a hairpin-like structure is known as a precursor of "hsa-miR-8072".

[0073] The term "hsa-miR-1233-5p gene" or "hsa-miR-1233-5p" used herein includes the hsa-miR-1233-5p gene (miRBase Accession No. MIMAT0022943) described in SEQ ID NO: 26, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1233-5p gene can be obtained by a method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336. Also, "hsa-mir-1233-1 and hsa-mir-1233-2" (miRBase Accession Nos. MI0006323 and MI0015973, SEQ ID NOs: 226 and 227) having a hairpin-like structure are known as precursors of "hsa-miR-1233-5p".

[0074] The term "hsa-miR-6887-5p gene" or "hsa-miR-6887-5p" used herein includes the hsa-miR-6887-5p gene (miRBase Accession No. MIMAT0027674) described in SEQ ID NO: 27, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6887-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6887" (miRBase Accession No. MI0022734, SEQ ID NO: 228) having a hairpin-like structure is known as a precursor of "hsa-miR-6887-5p".

[0075] The term "hsa-miR-1231 gene" or "hsa-miR-1231" used herein includes the hsa-miR-1231 gene (miRBase Accession No. MIMAT0005586) described in SEQ ID NO: 28, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1231 gene can be obtained by a method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336. Also, "hsa-mir-1231" (miRBase Accession No. MI0006321, SEQ ID NO: 229) having a hairpin-like structure is known as a precursor of "hsa-miR-1231".

[0076] The term "hsa-miR-5572 gene" or "hsa-miR-5572" used herein includes the hsa-miR-5572 gene (miRBase Accession No. MIMAT0022260) described in SEQ ID NO: 29, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-5572 gene can be obtained by a method described in Tandon M et al., 2012, Oral Dis, Vol. 18, p. 127-131. Also, "hsa-mir-5572" (miRBase Accession No. MI0019117, SEQ ID NO: 230) having a hairpin-like structure is known as a precursor of "hsa-miR-5572".

[0077] The term "hsa-miR-6738-5p gene" or "hsa-miR-6738-5p" used herein includes the hsa-miR-6738-5p gene (miRBase Accession No. MIMAT0027377) described in SEQ ID NO: 30, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6738-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6738" (miRBase Accession No. MI0022583, SEQ ID NO: 231) having a hairpin-like structure is known as a precursor of "hsa-miR-6738-5p".

[0078] The term "hsa-miR-6784-5p gene" or "hsa-miR-6784-5p" used herein includes the hsa-miR-6784-5p gene (miRBase Accession No. MIMAT0027468) described in SEQ ID NO: 31, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6784-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6784" (miRBase Accession No. MI0022629, SEQ ID NO: 232) having a hairpin-like structure is known as a precursor of "hsa-miR-6784-5p".

[0079] The term "hsa-miR-6791-5p gene" or "hsa-miR-6791-5p" used herein includes the hsa-miR-6791-5p gene (miRBase Accession No. MIMAT0027482) described in SEQ ID NO: 32, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6791-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6791" (miRBase Accession No. MI0022636, SEQ ID NO: 233) having a hairpin-like structure is known as a precursor of "hsa-miR-6791-5p".

[0080] The term "hsa-miR-6749-5p gene" or "hsa-miR-6749-5p" used herein includes the hsa-miR-6749-5p gene (miRBase Accession No. MIMAT0027398) described in SEQ ID NO: 33, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6749-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6749" (miRBase Accession No. MI0022594, SEQ ID NO: 234) having a hairpin-like structure is known as a precursor of "hsa-miR-6749-5p".

[0081]  The term "hsa-miR-6741-5p gene" or "hsa-miR-6741-5p" used herein includes the hsa-miR-6741-5p gene (miRBase Accession No. MIMAT0027383) described in SEQ ID NO: 34, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6741-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6741" (miRBase Accession No. MI0022586, SEQ ID NO: 235) having a hairpin-like structure is known as a precursor of "hsa-miR-6741-5p".

[0082] The term "hsa-miR-128-1-5p gene" or "hsa-miR-128-1-5p" used herein includes the hsa-miR-128-1-5p gene (miRBase Accession No. MIMAT0026477) described in SEQ ID NO: 35, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-128-1-5p gene can be obtained by a method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p. 735-739. Also, "hsa-mir-128-1" (miRBase Accession No. MI0000447, SEQ ID NO: 236) having a hairpin-like structure is known as a precursor of "hsa-miR-128-1-5p".

[0083] The term "hsa-miR-4419b gene" or "hsa-miR-4419b" used herein includes the hsa-miR-4419b gene (miRBase Accession No. MIMAT0019034) described in SEQ ID NO: 36, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4419b gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4419b" (miRBase Accession No. MI0016861, SEQ ID NO: 237) having a hairpin-like structure is known as a precursor of "hsa-miR-4419b".

[0084] The term "hsa-miR-6746-5p gene" or "hsa-miR-6746-5p" used herein includes the hsa-miR-6746-5p gene (miRBase Accession No. MIMAT0027392) described in SEQ ID NO: 37, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6746-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6746" (miRBase Accession No. MI0022591, SEQ ID NO: 238) having a hairpin-like structure is known as a precursor of "hsa-miR-6746-5p".

[0085] The term "hsa-miR-3184-5p gene" or "hsa-miR-3184-5p" used herein includes the hsa-miR-3184-5p gene (miRBase Accession No. MIMAT0015064) described in SEQ ID NO: 38, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3184-5p gene can be obtained by a method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Also, "hsa-mir-3184" (miRBase Accession No. MI0014226, SEQ ID NO: 239) having a hairpin-like structure is known as a precursor of "hsa-miR-3184-5p".

[0086] The term "hsa-miR-3679-5p gene" or "hsa-miR-3679-5p" used herein includes the hsa-miR-3679-5p gene (miRBase Accession No. MIMAT0018104) described in SEQ ID NO: 39, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3679-5p gene can be obtained by a method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Also, "hsa-mir-3679" (miRBase Accession No. MI0016080, SEQ ID NO: 240) having a hairpin-like structure is known as a precursor of "hsa-miR-3679-5p".

[0087] The term "hsa-miR-7110-5p gene" or "hsa-miR-7110-5p" used herein includes the hsa-miR-7110-5p gene (miRBase Accession No. MIMAT0028117) described in SEQ ID NO: 40, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-7110-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-7110" (miRBase Accession No. MI0022961, SEQ ID NO: 241) having a hairpin-like structure is known as a precursor of "hsa-miR-7110-5p".

[0088] The term "hsa-miR-4516 gene" or "hsa-miR-4516" used herein includes the hsa-miR-4516 gene (miRBase Accession No. MIMAT0019053) described in SEQ ID NO: 41, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4516 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4516" (miRBase Accession No. MI0016882, SEQ ID NO: 242) having a hairpin-like structure is known as a precursor of "hsa-miR-4516".

[0089] The term "hsa-miR-6717-5p gene" or "hsa-miR-6717-5p" used herein includes the hsa-miR-6717-5p gene (miRBase Accession No. MIMAT0025846) described in SEQ ID NO: 42, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6717-5p gene can be obtained by a method described in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. Also, "hsa-mir-6717" (miRBase Accession No. MI0022551, SEQ ID NO: 243) having a hairpin-like structure is known as a precursor of "hsa-miR-6717-5p".

[0090] The term "hsa-miR-6826-5p gene" or "hsa-miR-6826-5p" used herein includes the hsa-miR-6826-5p gene (miRBase Accession No. MIMAT0027552) described in SEQ ID NO: 43, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6826-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6826" (miRBase Accession No. MI0022671, SEQ ID NO: 244) having a hairpin-like structure is known as a precursor of "hsa-miR-6826-5p".

[0091] The term "hsa-miR-4433b-3p gene" or "hsa-miR-4433b-3p" used herein includes the hsa-miR-4433b-3p gene (miRBase Accession No. MIMAT0030414) described in SEQ ID NO: 44, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4433b-3p gene can be obtained by a method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Also, "hsa-mir-4433b" (miRBase Accession No. MI0025511, SEQ ID NO: 245) having a hairpin-like structure is known as a precursor of "hsa-miR-4433b-3p".

[0092] The term "hsa-miR-3679-3p gene" or "hsa-miR-3679-3p" used herein includes the hsa-miR-3679-3p gene (miRBase Accession No. MIMAT0018105) described in SEQ ID NO: 45, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3679-3p gene can be obtained by a method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Also, "hsa-mir-3679" (miRBase Accession No. MI0016080, SEQ ID NO: 240) having a hairpin-like structure is known as a precursor of "hsa-miR-3679-3p".

[0093] The term "hsa-miR-3135b gene" or "hsa-miR-3135b" used herein includes the hsa-miR-3135b gene (miRBase Accession No. MIMAT0018985) described in SEQ ID NO: 46, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3135b gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-3135b" (miRBase Accession No. MI0016809, SEQ ID NO: 246) having a hairpin-like structure is known as a precursor of "hsa-miR-3135b".

[0094] The term "hsa-miR-3622a-5p gene" or "hsa-miR-3622a-5p" used herein includes the hsa-miR-3622a-5p gene (miRBase Accession No. MIMAT0018003) described in SEQ ID NO: 47, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3622a-5p gene can be obtained by a method described in Witten D et al., 2010, BMC Biol, Vol. 8, p. 58. Also, "hsa-mir-3622a" (miRBase Accession No. MI0016013, SEQ ID NO: 247) having a hairpin-like structure is known as a precursor of "hsa-miR-3622a-5p".

[0095] The term "hsa-miR-711 gene" or "hsa-miR-711" used herein includes the hsa-miR-711 gene (miRBase Accession No. MIMAT0012734) described in SEQ ID NO: 48, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-711 gene can be obtained by a method described in Artzi S et al., 2008, BMC Bioinformatics, Vol. 9, p. 39. Also, "hsa-mir-711" (miRBase Accession No. MI0012488, SEQ ID NO: 248) having a hairpin-like structure is known as a precursor of "hsa-miR-711".

[0096] The term "hsa-miR-4467 gene" or "hsa-miR-4467" used herein includes the hsa-miR-4467 gene (miRBase Accession No. MIMAT0018994) described in SEQ ID NO: 49, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4467 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4467" (miRBase Accession No. MI0016818, SEQ ID NO: 249) having a hairpin-like structure is known as a precursor of "hsa-miR-4467".

[0097] The term "hsa-miR-6857-5p gene" or "hsa-miR-6857-5p" used herein includes the hsa-miR-6857-5p gene (miRBase Accession No. MIMAT0027614) described in SEQ ID NO: 50, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6857-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6857" (miRBase Accession No. MI0022703, SEQ ID NO: 250) having a hairpin-like structure is known as a precursor of "hsa-miR-6857-5p".

[0098] The term "hsa-miR-6515-3p gene" or "hsa-miR-6515-3p" used herein includes the hsa-miR-6515-3p gene (miRBase Accession No. MIMAT0025487) described in SEQ ID NO: 51, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6515-3p gene can be obtained by a method described in Joyce CE et al., 2011, Hum Mol Genet, Vol. 20, p. 4025-4040. Also, "hsa-mir-6515" (miRBase Accession No. MI0022227, SEQ ID NO: 251) having a hairpin-like structure is known as a precursor of "hsa-miR-6515-3p".

[0099] The term "hsa-miR-1225-5p gene" or "hsa-miR-1225-5p" used herein includes the hsa-miR-1225-5p gene (miRBase Accession No. MIMAT0005572) described in SEQ ID NO: 52, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1225-5p gene can be obtained by a method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336. Also, "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 206) having a hairpin-like structure is known as a precursor of "hsa-miR-1225-5p".

[0100] The term "hsa-miR-187-5p gene" or "hsa-miR-187-5p" used herein includes the hsa-miR-187-5p gene (miRBase Accession No. MIMAT0004561) described in SEQ ID NO: 53, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-187-5p gene can be obtained by a method described in Lim LP et al., 2003, Science, Vol. 299, p. 1540. Also, "hsa-mir-187" (miRBase Accession No. MI0000274, SEQ ID NO: 252) having a hairpin-like structure is known as a precursor of "hsa-miR-187-5p".

[0101] The term "hsa-miR-3185 gene" or "hsa-miR-3185" used herein includes the hsa-miR-3185 gene (miRBase Accession No. MIMAT0015065) described in SEQ ID NO: 54, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3185 gene can be obtained by a method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Also, "hsa-mir-3185" (miRBase Accession No. MI0014227, SEQ ID NO: 253) having a hairpin-like structure is known as a precursor of "hsa-miR-3185".

[0102] The term "hsa-miR-642b-3p gene" or "hsa-miR-642b-3p" used herein includes the hsa-miR-642b-3p gene (miRBase Accession No. MIMAT0018444) described in SEQ ID NO: 55, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-642b-3p gene can be obtained by a method described in Witten D et al., 2010, BMC Biol, Vol. 8, p. 58. Also, "hsa-mir-642b" (miRBase Accession No. MI0016685, SEQ ID NO: 254) having a hairpin-like structure is known as a precursor of "hsa-miR-642b-3p".

[0103]  The term "hsa-miR-1249 gene" or "hsa-miR-1249" used herein includes the hsa-miR-1249 gene (miRBase Accession No. MIMAT0005901) described in SEQ ID NO: 56, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1249 gene can be obtained by a method described in Morin RD et al., 2008, Genome Res, Vol. 18, p. 610-621. Also, "hsa-mir-1249" (miRBase Accession No. MI0006384, SEQ ID NO: 255) having a hairpin-like structure is known as a precursor of "hsa-miR-1249".

[0104] The term "hsa-miR-744-5p gene" or "hsa-miR-744-5p" used herein includes the hsa-miR-744-5p gene (miRBase Accession No. MIMAT0004945) described in SEQ ID NO: 57, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-744-5p gene can be obtained by a method described in Berezikov E et al., 2006, Genome Res, Vol. 16, p. 1289-1298. Also, "hsa-mir-744" (miRBase Accession No. MI0005559, SEQ ID NO: 256) having a hairpin-like structure is known as a precursor of "hsa-miR-744-5p".

[0105] The term "hsa-miR-4442 gene" or "hsa-miR-4442" used herein includes the hsa-miR-4442 gene (miRBase Accession No. MIMAT0018960) described in SEQ ID NO: 58, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4442 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4442" (miRBase Accession No. MI0016785, SEQ ID NO: 257) having a hairpin-like structure is known as a precursor of "hsa-miR-4442".

[0106] The term "hsa-miR-1228-3p gene" or "hsa-miR-1228-3p" used herein includes the hsa-miR-1228-3p gene (miRBase Accession No. MIMAT0005583) described in SEQ ID NO: 59, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1228-3p gene can be obtained by a method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336. Also, "hsa-mir-1228" (miRBase Accession No. MI0006318, SEQ ID NO: 258) having a hairpin-like structure is known as a precursor of "hsa-miR-1228-3p".

[0107] The term "hsa-miR-939-5p gene" or "hsa-miR-939-5p" used herein includes the hsa-miR-939-5p gene (miRBase Accession No. MIMAT0004982) described in SEQ ID NO: 60, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-939-5p gene can be obtained by a method described in Lui WO et al., 2007, Cancer Res, Vol. 67, p. 6031-6043. Also, "hsa-mir-939" (miRBase Accession No. MI0005761, SEQ ID NO: 259) having a hairpin-like structure is known as a precursor of "hsa-miR-939-5p".

[0108] The term "hsa-miR-6845-5p gene" or "hsa-miR-6845-5p" used herein includes the hsa-miR-6845-5p gene (miRBase Accession No. MIMAT0027590) described in SEQ ID NO: 61, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6845-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6845" (miRBase Accession No. MI0022691, SEQ ID NO: 260) having a hairpin-like structure is known as a precursor of "hsa-miR-6845-5p".

[0109] The term "hsa-miR-887-3p gene" or "hsa-miR-887-3p" used herein includes the hsa-miR-887-3p gene (miRBase Accession No. MIMAT0004951) described in SEQ ID NO: 62, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-887-3p gene can be obtained by a method described in Berezikov E et al., 2006, Genome Res, Vol. 16, p. 1289-1298. Also, "hsa-mir-887" (miRBase Accession No. MI0005562, SEQ ID NO: 261) having a hairpin-like structure is known as a precursor of "hsa-miR-887-3p".

[0110] The term "hsa-miR-7845-5p gene" or "hsa-miR-7845-5p" used herein includes the hsa-miR-7845-5p gene (miRBase Accession No. MIMAT0030420) described in SEQ ID NO: 63, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-7845-5p gene can be obtained by a method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Also, "hsa-mir-7845" (miRBase Accession No. MI0025515, SEQ ID NO: 262) having a hairpin-like structure is known as a precursor of "hsa-miR-7845-5p".

[0111] The term "hsa-miR-6729-5p gene" or "hsa-miR-6729-5p" used herein includes the hsa-miR-6729-5p gene (miRBase Accession No. MIMAT0027359) described in SEQ ID NO: 64, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6729-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6729" (miRBase Accession No. MI0022574, SEQ ID NO: 263) having a hairpin-like structure is known as a precursor of "hsa-miR-6729-5p".

[0112] The term "hsa-miR-4632-5p gene" or "hsa-miR-4632-5p" used herein includes the hsa-miR-4632-5p gene (miRBase Accession No. MIMAT0022977) described in SEQ ID NO: 65, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4632-5p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4632" (miRBase Accession No. MI0017259, SEQ ID NO: 264) having a hairpin-like structure is known as a precursor of "hsa-miR-4632-5p".

[0113] The term "hsa-miR-615-5p gene" or "hsa-miR-615-5p" used herein includes the hsa-miR-615-5p gene (miRBase Accession No. MIMAT0004804) described in SEQ ID NO: 66, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-615-5p gene can be obtained by a method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, p. 3687-3692. Also, "hsa-mir-615" (miRBase Accession No. MI0003628, SEQ ID NO: 265) having a hairpin-like structure is known as a precursor of "hsa-miR-615-5p".

[0114] The term "hsa-miR-6724-5p gene" or "hsa-miR-6724-5p" used herein includes the hsa-miR-6724-5p gene (miRBase Accession No. MIMAT0025856) described in SEQ ID NO: 67, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6724-5p gene can be obtained by a method described in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. Also, "hsa-mir-6724" (miRBase Accession No. MI0022559, SEQ ID NO: 266) having a hairpin-like structure is known as a precursor of "hsa-miR-6724-5p".

[0115] The term "hsa-miR-4728-5p gene" or "hsa-miR-4728-5p" used herein includes the hsa-miR-4728-5p gene (miRBase Accession No. MIMAT0019849) described in SEQ ID NO: 68, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4728-5p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4728" (miRBase Accession No. MI0017365, SEQ ID NO: 267) having a hairpin-like structure is known as a precursor of "hsa-miR-4728-5p".

[0116] The term "hsa-miR-6732-5p gene" or "hsa-miR-6732-5p" used herein includes the hsa-miR-6732-5p gene (miRBase Accession No. MIMAT0027365) described in SEQ ID NO: 69, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6732-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6732" (miRBase Accession No. MI0022577, SEQ ID NO: 268) having a hairpin-like structure is known as a precursor of "hsa-miR-6732-5p".

[0117] The term "hsa-miR-6816-5p gene" or "hsa-miR-6816-5p" used herein includes the hsa-miR-6816-5p gene (miRBase Accession No. MIMAT0027532) described in SEQ ID NO: 70, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6816-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6816" (miRBase Accession No. MI0022661, SEQ ID NO: 269) having a hairpin-like structure is known as a precursor of "hsa-miR-6816-5p".

[0118] The term "hsa-miR-4695-5p gene" or "hsa-miR-4695-5p" used herein includes the hsa-miR-4695-5p gene (miRBase Accession No. MIMAT0019788) described in SEQ ID NO: 71, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4695-5p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4695" (miRBase Accession No. MI0017328, SEQ ID NO: 270) having a hairpin-like structure is known as a precursor of "hsa-miR-4695-5p".

[0119] The term "hsa-miR-6088 gene" or "hsa-miR-6088" used herein includes the hsa-miR-6088 gene (miRBase Accession No. MIMAT0023713) described in SEQ ID NO: 72, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6088 gene can be obtained by a method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, p. 2049-2057. Also, "hsa-mir-6088" (miRBase Accession No. MI0020365, SEQ ID NO: 271) having a hairpin-like structure is known as a precursor of "hsa-miR-6088".

[0120] The term "hsa-miR-7975 gene" or "hsa-miR-7975" used herein includes the hsa-miR-7975 gene (miRBase Accession No. MIMAT0031178) described in SEQ ID NO: 73, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-7975 gene can be obtained by a method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, online. Also, "hsa-mir-7975" (miRBase Accession No. MI0025751, SEQ ID NO: 272) having a hairpin-like structure is known as a precursor of "hsa-miR-7975".

[0121] The term "hsa-miR-3197 gene" or "hsa-miR-3197" used herein includes the hsa-miR-3197 gene (miRBase Accession No. MIMAT0015082) described in SEQ ID NO: 74, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3197 gene can be obtained by a method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Also, "hsa-mir-3197" (miRBase Accession No. MI0014245, SEQ ID NO: 273) having a hairpin-like structure is known as a precursor of "hsa-miR-3197".

[0122] The term "hsa-miR-6125 gene" or "hsa-miR-6125" used herein includes the hsa-miR-6125 gene (miRBase Accession No. MIMAT0024598) described in SEQ ID NO: 75, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6125 gene can be obtained by a method described in Smith JL et al., 2012, J Virol, Vol. 86, p. 5278-5287. Also, "hsa-mir-6125" (miRBase Accession No. MI0021259, SEQ ID NO: 274) having a hairpin-like structure is known as a precursor of "hsa-miR-6125".

[0123] The term "hsa-miR-4433-3p gene" or "hsa-miR-4433-3p" used herein includes the hsa-miR-4433-3p gene (miRBase Accession No. MIMAT0018949) described in SEQ ID NO: 76, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4433-3p gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4433" (miRBase Accession No. MI0016773, SEQ ID NO: 275) having a hairpin-like structure is known as a precursor of "hsa-miR-4433-3p".

[0124] The term "hsa-miR-6727-5p gene" or "hsa-miR-6727-5p" used herein includes the hsa-miR-6727-5p gene (miRBase Accession No. MIMAT0027355) described in SEQ ID NO: 77, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6727-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6727" (miRBase Accession No. MI0022572, SEQ ID NO: 276) having a hairpin-like structure is known as a precursor of "hsa-miR-6727-5p".

[0125]  The term "hsa-miR-4706 gene" or "hsa-miR-4706" used herein includes the hsa-miR-4706 gene (miRBase Accession No. MIMAT0019806) described in SEQ ID NO: 78, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4706 gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4706" (miRBase Accession No. MI0017339, SEQ ID NO: 277) having a hairpin-like structure is known as a precursor of "hsa-miR-4706".

[0126] The term "hsa-miR-7847-3p gene" or "hsa-miR-7847-3p" used herein includes the hsa-miR-7847-3p gene (miRBase Accession No. MIMAT0030422) described in SEQ ID NO: 79, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-7847-3p gene can be obtained by a method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Also, "hsa-mir-7847" (miRBase Accession No. MI0025517, SEQ ID NO: 278) having a hairpin-like structure is known as a precursor of "hsa-miR-7847-3p".

[0127] The term "hsa-miR-6805-3p gene" or "hsa-miR-6805-3p" used herein includes the hsa-miR-6805-3p gene (miRBase Accession No. MIMAT0027511) described in SEQ ID NO: 80, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6805-3p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6805" (miRBase Accession No. MI0022650, SEQ ID NO: 279) having a hairpin-like structure is known as a precursor of "hsa-miR-6805-3p".

[0128] The term "hsa-miR-6766-3p gene" or "hsa-miR-6766-3p" used herein includes the hsa-miR-6766-3p gene (miRBase Accession No. MIMAT0027433) described in SEQ ID NO: 81, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6766-3p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6766" (miRBase Accession No. MI0022611, SEQ ID NO: 280) having a hairpin-like structure is known as a precursor of "hsa-miR-6766-3p".

[0129] The term "hsa-miR-1913 gene" or "hsa-miR-1913" used herein includes the hsa-miR-1913 gene (miRBase Accession No. MIMAT0007888) described in SEQ ID NO: 82, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1913 gene can be obtained by a method described in Bar M et al., 2008, Stem Cells, Vol. 26, p. 2496-2505. Also, "hsa-mir-1913" (miRBase Accession No. MI0008334, SEQ ID NO: 281) having a hairpin-like structure is known as a precursor of "hsa-miR-1913".

[0130] The term "hsa-miR-4649-5p gene" or "hsa-miR-4649-5p" used herein includes the hsa-miR-4649-5p gene (miRBase Accession No. MIMAT0019711) described in SEQ ID NO: 83, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4649-5p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4649" (miRBase Accession No. MI0017276, SEQ ID NO: 282) having a hairpin-like structure is known as a precursor of "hsa-miR-4649-5p".

[0131] The term "hsa-miR-602 gene" or "hsa-miR-602" used herein includes the hsa-miR-602 gene (miRBase Accession No. MIMAT0003270) described in SEQ ID NO: 84, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-602 gene can be obtained by a method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, Vol. 103, p. 3687-3692. Also, "hsa-mir-602" (miRBase Accession No. MI0003615, SEQ ID NO: 283) having a hairpin-like structure is known as a precursor of "hsa-miR-602".

[0132] The term "hsa-miR-3663-3p gene" or "hsa-miR-3663-3p" used herein includes the hsa-miR-3663-3p gene (miRBase Accession No. MIMAT0018085) described in SEQ ID NO: 85, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3663-3p gene can be obtained by a method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. Also, "hsa-mir-3663" (miRBase Accession No. MI0016064, SEQ ID NO: 284) having a hairpin-like structure is known as a precursor of "hsa-miR-3663-3p".

[0133] The term "hsa-miR-6893-5p gene" or "hsa-miR-6893-5p" used herein includes the hsa-miR-6893-5p gene (miRBase Accession No. MIMAT0027686) described in SEQ ID NO: 86, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6893-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6893" (miRBase Accession No. MI0022740, SEQ ID NO: 285) having a hairpin-like structure is known as a precursor of "hsa-miR-6893-5p".

[0134] The term "hsa-miR-6861-5p gene" or "hsa-miR-6861-5p" used herein includes the hsa-miR-6861-5p gene (miRBase Accession No. MIMAT0027623) described in SEQ ID NO: 87, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6861-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6861" (miRBase Accession No. MI0022708, SEQ ID NO: 286) having a hairpin-like structure is known as a precursor of "hsa-miR-6861-5p".

[0135] The term "hsa-miR-4449 gene" or "hsa-miR-4449" used herein includes the hsa-miR-4449 gene (miRBase Accession No. MIMAT0018968) described in SEQ ID NO: 88, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4449 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4449" (miRBase Accession No. MI0016792, SEQ ID NO: 287) having a hairpin-like structure is known as a precursor of "hsa-miR-4449".

[0136] The term "hsa-miR-6842-5p gene" or "hsa-miR-6842-5p" used herein includes the hsa-miR-6842-5p gene (miRBase Accession No. MIMAT0027586) described in SEQ ID NO: 89, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6842-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6842" (miRBase Accession No. MI0022688, SEQ ID NO: 288) having a hairpin-like structure is known as a precursor of "hsa-miR-6842-5p".

[0137] The term "hsa-miR-4454 gene" or "hsa-miR-4454" used herein includes the hsa-miR-4454 gene (miRBase Accession No. MIMAT0018976) described in SEQ ID NO: 90, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4454 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4454" (miRBase Accession No. MI0016800, SEQ ID NO: 289) having a hairpin-like structure is known as a precursor of "hsa-miR-4454".

[0138] The term "hsa-miR-5195-3p gene" or "hsa-miR-5195-3p" used herein includes the hsa-miR-5195-3p gene (miRBase Accession No. MIMAT0021127) described in SEQ ID NO: 91, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-5195-3p gene can be obtained by a method described in Schotte D et al., 2011, Leukemia, Vol. 25, p. 1389-1399. Also, "hsa-mir-5195" (miRBase Accession No. MI0018174, SEQ ID NO: 290) having a hairpin-like structure is known as a precursor of "hsa-miR-5195-3p".

[0139] The term "hsa-miR-663b gene" or "hsa-miR-663b" used herein includes the hsa-miR-663b gene (miRBase Accession No. MIMAT0005867) described in SEQ ID NO: 92, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-663b gene can be obtained by a method described in Takada S et al., 2008, Leukemia, Vol. 22, p. 1274-1278. Also, "hsa-mir-663b" (miRBase Accession No. MI0006336, SEQ ID NO: 291) having a hairpin-like structure is known as a precursor of "hsa-miR-663b".

[0140] The term "hsa-miR-6765-5p gene" or "hsa-miR-6765-5p" used herein includes the hsa-miR-6765-5p gene (miRBase Accession No. MIMAT0027430) described in SEQ ID NO: 93, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6765-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 292) having a hairpin-like structure is known as a precursor of "hsa-miR-6765-5p".

[0141] The term "hsa-miR-4513 gene" or "hsa-miR-4513" used herein includes the hsa-miR-4513 gene (miRBase Accession No. MIMAT0019050) described in SEQ ID NO: 94, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4513 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4513" (miRBase Accession No. MI0016879, SEQ ID NO: 293) having a hairpin-like structure is known as a precursor of "hsa-miR-4513".

[0142] The term "hsa-miR-614 gene" or "hsa-miR-614" used herein includes the hsa-miR-614 gene (miRBase Accession No. MIMAT0003282) described in SEQ ID NO: 95, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-614 gene can be obtained by a method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, Vol. 103, p. 3687-3692. Also, "hsa-mir-614" (miRBase Accession No. MI0003627, SEQ ID NO: 294) having a hairpin-like structure is known as a precursor of "hsa-miR-614".

[0143] The term "hsa-miR-6785-5p gene" or "hsa-miR-6785-5p" used herein includes the hsa-miR-6785-5p gene (miRBase Accession No. MIMAT0027470) described in SEQ ID NO: 96, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6785-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6785" (miRBase Accession No. MI0022630, SEQ ID NO: 295) having a hairpin-like structure is known as a precursor of "hsa-miR-6785-5p".

[0144] The term "hsa-miR-6777-5p gene" or "hsa-miR-6777-5p" used herein includes the hsa-miR-6777-5p gene (miRBase Accession No. MIMAT0027454) described in SEQ ID NO: 97, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6777-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6777" (miRBase Accession No. MI0022622, SEQ ID NO: 296) having a hairpin-like structure is known as a precursor of "hsa-miR-6777-5p".

[0145] The term "hsa-miR-940 gene" or "hsa-miR-940" used herein includes the hsa-miR-940 gene (miRBase Accession No. MIMAT0004983) described in SEQ ID NO: 98, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-940 gene can be obtained by a method described in Lui WO et al., 2007, Cancer Res, Vol. 67, p. 6031-6043. Also, "hsa-mir-940" (miRBase Accession No. MI0005762, SEQ ID NO: 297) having a hairpin-like structure is known as a precursor of "hsa-miR-940".

[0146] The term "hsa-miR-4741 gene" or "hsa-miR-4741" used herein includes the hsa-miR-4741 gene (miRBase Accession No. MIMAT0019871) described in SEQ ID NO: 99, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4741 gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4741" (miRBase Accession No. MI0017379, SEQ ID NO: 298) having a hairpin-like structure is known as a precursor of "hsa-miR-4741".

[0147]  The term "hsa-miR-6870-5p gene" or "hsa-miR-6870-5p" used herein includes the hsa-miR-6870-5p gene (miRBase Accession No. MIMAT0027640) described in SEQ ID NO: 100, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6870-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6870" (miRBase Accession No. MI0022717, SEQ ID NO: 299) having a hairpin-like structure is known as a precursor of "hsa-miR-6870-5p".

[0148] The term "hsa-miR-6131 gene" or "hsa-miR-6131" used herein includes the hsa-miR-6131 gene (miRBase Accession No. MIMAT0024615) described in SEQ ID NO: 101, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6131 gene can be obtained by a method described in Dannemann M et al., 2012, Genome Biol Evol, Vol. 4, p. 552-564. Also, "hsa-mir-6131" (miRBase Accession No. MI0021276, SEQ ID NO: 300) having a hairpin-like structure is known as a precursor of "hsa-miR-6131".

[0149] The term "hsa-miR-150-3p gene" or "hsa-miR-150-3p" used herein includes the hsa-miR-150-3p gene (miRBase Accession No. MIMAT0004610) described in SEQ ID NO: 102, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-150-3p gene can be obtained by a method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p. 735-739. Also, "hsa-mir-150" (miRBase Accession No. MI0000479, SEQ ID NO: 301) having a hairpin-like structure is known as a precursor of "hsa-miR-150-3p".

[0150] The term "hsa-miR-4707-5p gene" or "hsa-miR-4707-5p" used herein includes the hsa-miR-4707-5p gene (miRBase Accession No. MIMAT0019807) described in SEQ ID NO: 103, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4707-5p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4707" (miRBase Accession No. MI0017340, SEQ ID NO: 302) having a hairpin-like structure is known as a precursor of "hsa-miR-4707-5p".

[0151] The term "hsa-miR-1915-3p gene" or "hsa-miR-1915-3p" used herein includes the hsa-miR-1915-3p gene (miRBase Accession No. MIMAT0007892) described in SEQ ID NO: 104, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1915-3p gene can be obtained by a method described in Bar M et al., 2008, Stem Cells, Vol. 26, p. 2496-2505. Also, "hsa-mir-1915" (miRBase Accession No. MI0008336, SEQ ID NO: 303) having a hairpin-like structure is known as a precursor of "hsa-miR-1915-3p".

[0152] The term "hsa-miR-3937 gene" or "hsa-miR-3937" used herein includes the hsa-miR-3937 gene (miRBase Accession No. MIMAT0018352) described in SEQ ID NO: 105, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3937 gene can be obtained by a method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. Also, "hsa-mir-3937" (miRBase Accession No. MI0016593, SEQ ID NO: 304) having a hairpin-like structure is known as a precursor of "hsa-miR-3937".

[0153] The term "hsa-miR-937-5p gene" or "hsa-miR-937-5p" used herein includes the hsa-miR-937-5p gene (miRBase Accession No. MIMAT0022938) described in SEQ ID NO: 106, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-937-5p gene can be obtained by a method described in Lui WO et al., 2007, Cancer Res, Vol. 67, p. 6031-6043. Also, "hsa-mir-937" (miRBase Accession No. MI0005759, SEQ ID NO: 305) having a hairpin-like structure is known as a precursor of "hsa-miR-937-5p".

[0154] The term "hsa-miR-4443 gene" or "hsa-miR-4443" used herein includes the hsa-miR-4443 gene (miRBase Accession No. MIMAT0018961) described in SEQ ID NO: 107, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4443 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4443" (miRBase Accession No. MI0016786, SEQ ID NO: 306) having a hairpin-like structure is known as a precursor of "hsa-miR-4443".

[0155] The term "hsa-miR-1914-3p gene" or "hsa-miR-1914-3p" used herein includes the hsa-miR-1914-3p gene (miRBase Accession No. MIMAT0007890) described in SEQ ID NO: 108, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1914-3p gene can be obtained by a method described in Bar M et al., 2008, Stem Cells, Vol. 26, p. 2496-2505. Also, "hsa-mir-1914" (miRBase Accession No. MI0008335, SEQ ID NO: 307) having a hairpin-like structure is known as a precursor of "hsa-miR-1914-3p".

[0156] The term "hsa-miR-3620-5p gene" or "hsa-miR-3620-5p" used herein includes the hsa-miR-3620-5p gene (miRBase Accession No. MIMAT0022967) described in SEQ ID NO: 109, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3620-5p gene can be obtained by a method described in Witten D et al., 2010, BMC Biol, Vol. 8, p. 58. Also, "hsa-mir-3620" (miRBase Accession No. MI0016011, SEQ ID NO: 308) having a hairpin-like structure is known as a precursor of "hsa-miR-3620-5p".

[0157] The term "hsa-miR-1268b gene" or "hsa-miR-1268b" used herein includes the hsa-miR-1268b gene (miRBase Accession No. MIMAT0018925) described in SEQ ID NO: 110, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1268b gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-1268b" (miRBase Accession No. MI0016748, SEQ ID NO: 309) having a hairpin-like structure is known as a precursor of "hsa-miR-1268b".

[0158] The term "hsa-miR-1227-5p gene" or "hsa-miR-1227-5p" used herein includes the hsa-miR-1227-5p gene (miRBase Accession No. MIMAT0022941) described in SEQ ID NO: 111, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1227-5p gene can be obtained by a method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336. Also, "hsa-mir-1227" (miRBase Accession No. MI0006316, SEQ ID NO: 310) having a hairpin-like structure is known as a precursor of "hsa-miR-1227-5p".

[0159] The term "hsa-miR-6880-5p gene" or "hsa-miR-6880-5p" used herein includes the hsa-miR-6880-5p gene (miRBase Accession No. MIMAT0027660) described in SEQ ID NO: 112, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6880-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6880" (miRBase Accession No. MI0022727, SEQ ID NO: 311) having a hairpin-like structure is known as a precursor of "hsa-miR-6880-5p".

[0160] The term "hsa-miR-4417 gene" or "hsa-miR-4417" used herein includes the hsa-miR-4417 gene (miRBase Accession No. MIMAT0018929) described in SEQ ID NO: 113, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4417 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4417" (miRBase Accession No. MI0016753, SEQ ID NO: 312) having a hairpin-like structure is known as a precursor of "hsa-miR-4417".

[0161] The term "hsa-miR-6802-5p gene" or "hsa-miR-6802-5p" used herein includes the hsa-miR-6802-5p gene (miRBase Accession No. MIMAT0027504) described in SEQ ID NO: 114, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6802-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6802" (miRBase Accession No. MI0022647, SEQ ID NO: 313) having a hairpin-like structure is known as a precursor of "hsa-miR-6802-5p".

[0162] The term "hsa-miR-6769a-5p gene" or "hsa-miR-6769a-5p" used herein includes the hsa-miR-6769a-5p gene (miRBase Accession No. MIMAT0027438) described in SEQ ID NO: 115, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6769a-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6769a" (miRBase Accession No. MI0022614, SEQ ID NO: 314) having a hairpin-like structure is known as a precursor of "hsa-miR-6769a-5p".

[0163] The term "hsa-miR-663a gene" or "hsa-miR-663a" used herein includes the hsa-miR-663a gene (miRBase Accession No. MIMAT0003326) described in SEQ ID NO: 116, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-663a gene can be obtained by a method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, Vol. 103, p. 3687-3692. Also, "hsa-mir-663a" (miRBase Accession No. MI0003672, SEQ ID NO: 315) having a hairpin-like structure is known as a precursor of "hsa-miR-663a".

[0164] The term "hsa-miR-6721-5p gene" or "hsa-miR-6721-5p" used herein includes the hsa-miR-6721-5p gene (miRBase Accession No. MIMAT0025852) described in SEQ ID NO: 117, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6721-5p gene can be obtained by a method described in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. Also, "hsa-mir-6721" (miRBase Accession No. MI0022556, SEQ ID NO: 316) having a hairpin-like structure is known as a precursor of "hsa-miR-6721-5p".

[0165] The term "hsa-miR-4532 gene" or "hsa-miR-4532" used herein includes the hsa-miR-4532 gene (miRBase Accession No. MIMAT0019071) described in SEQ ID NO: 118, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4532 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4532" (miRBase Accession No. MI0016899, SEQ ID NO: 317) having a hairpin-like structure is known as a precursor of "hsa-miR-4532".

[0166] The term "hsa-miR-7977 gene" or "hsa-miR-7977" used herein includes the hsa-miR-7977 gene (miRBase Accession No. MIMAT0031180) described in SEQ ID NO: 119, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-7977 gene can be obtained by a method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, online. Also, "hsa-mir-7977" (miRBase Accession No. MI0025753, SEQ ID NO: 318) having a hairpin-like structure is known as a precursor of "hsa-miR-7977".

[0167] The term "hsa-miR-92b-5p gene" or "hsa-miR-92b-5p" used herein includes the hsa-miR-92b-5p gene (miRBase Accession No. MIMAT0004792) described in SEQ ID NO: 120, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-92b-5p gene can be obtained by a method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, Vol. 103, p. 3687-3692. Also, "hsa-mir-92b" (miRBase Accession No. MI0003560, SEQ ID NO: 319) having a hairpin-like structure is known as a precursor of "hsa-miR-92b-5p".

[0168] The term "hsa-miR-371a-5p gene" or "hsa-miR-371a-5p" used herein includes the hsa-miR-371a-5p gene (miRBase Accession No. MIMAT0004687) described in SEQ ID NO: 121, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-371a-5p gene can be obtained by a method described in Suh MR et al., 2004, Dev Biol, Vol. 270, p. 488-498. Also, "hsa-mir-371a" (miRBase Accession No. MI0000779, SEQ ID NO: 320) having a hairpin-like structure is known as a precursor of "hsa-miR-371a-5p".

[0169]  The term "hsa-miR-6126 gene" or "hsa-miR-6126" used herein includes the hsa-miR-6126 gene (miRBase Accession No. MIMAT0024599) described in SEQ ID NO: 122, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6126 gene can be obtained by a method described in Smith JL et al., 2012, J Virol, Vol. 86, p. 5278-5287. Also, "hsa-mir-6126" (miRBase Accession No. MI0021260, SEQ ID NO: 321) having a hairpin-like structure is known as a precursor of "hsa-miR-6126".

[0170] The term "hsa-miR-4734 gene" or "hsa-miR-4734" used herein includes the hsa-miR-4734 gene (miRBase Accession No. MIMAT0019859) described in SEQ ID NO: 123, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4734 gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4734" (miRBase Accession No. MI0017371, SEQ ID NO: 322) having a hairpin-like structure is known as a precursor of "hsa-miR-4734".

[0171] The term "hsa-miR-4665-3p gene" or "hsa-miR-4665-3p" used herein includes the hsa-miR-4665-3p gene (miRBase Accession No. MIMAT0019740) described in SEQ ID NO: 124, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4665-3p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4665" (miRBase Accession No. MI0017295, SEQ ID NO: 323) having a hairpin-like structure is known as a precursor of "hsa-miR-4665-3p".

[0172] The term "hsa-miR-423-5p gene" or "hsa-miR-423-5p" used herein includes the hsa-miR-423-5p gene (miRBase Accession No. MIMAT0004748) described in SEQ ID NO: 125, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-423-5p gene can be obtained by a method described in Kasashima K et al., 2004, Biochem Biophys Res Commun, Vol. 322, p. 403-410. Also, "hsa-mir-423" (miRBase Accession No. MI0001445, SEQ ID NO: 324) having a hairpin-like structure is known as a precursor of "hsa-miR-423-5p".

[0173] The term "hsa-miR-1469 gene" or "hsa-miR-1469" used herein includes the hsa-miR-1469 gene (miRBase Accession No. MIMAT0007347) described in SEQ ID NO: 126, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1469 gene can be obtained by a method described in Kawaji H et al., 2008, BMC Genomics, Vol. 9, p. 157. Also, "hsa-mir-1469" (miRBase Accession No. MI0007074, SEQ ID NO: 325) having a hairpin-like structure is known as a precursor of "hsa-miR-1469".

[0174] The term "hsa-miR-4675 gene" or "hsa-miR-4675" used herein includes the hsa-miR-4675 gene (miRBase Accession No. MIMAT0019757) described in SEQ ID NO: 127, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4675 gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4675" (miRBase Accession No. MI0017306, SEQ ID NO: 326) having a hairpin-like structure is known as a precursor of "hsa-miR-4675".

[0175] The term "hsa-miR-1915-5p gene" or "hsa-miR-1915-5p" used herein includes the hsa-miR-1915-5p gene (miRBase Accession No. MIMAT0007891) described in SEQ ID NO: 128, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1915-5p gene can be obtained by a method described in Bar M et al., 2008, Stem Cells, Vol. 26, p. 2496-2505. Also, "hsa-mir-1915" (miRBase Accession No. MI0008336, SEQ ID NO: 303) having a hairpin-like structure is known as a precursor of "hsa-miR-1915-5p".

[0176] The term "hsa-miR-6716-5p gene" or "hsa-miR-6716-5p" used herein includes the hsa-miR-6716-5p gene (miRBase Accession No. MIMAT0025844) described in SEQ ID NO: 129, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6716-5p gene can be obtained by a method described in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. Also, "hsa-mir-6716" (miRBase Accession No. MI0022550, SEQ ID NO: 327) having a hairpin-like structure is known as a precursor of "hsa-miR-6716-5p".

[0177] The term "hsa-miR-718 gene" or "hsa-miR-718" used herein includes the hsa-miR-718 gene (miRBase Accession No. MIMAT0012735) described in SEQ ID NO: 130, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-718 gene can be obtained by a method described in Artzi S et al., 2008, BMC Bioinformatics, Vol. 9, p. 39. Also, "hsa-mir-718" (miRBase Accession No. MI0012489, SEQ ID NO: 328) having a hairpin-like structure is known as a precursor of "hsa-miR-718".

[0178] The term "hsa-miR-4281 gene" or "hsa-miR-4281" used herein includes the hsa-miR-4281 gene (miRBase Accession No. MIMAT0016907) described in SEQ ID NO: 131, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4281 gene can be obtained by a method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Also, "hsa-mir-4281" (miRBase Accession No. MI0015885, SEQ ID NO: 329) having a hairpin-like structure is known as a precursor of "hsa-miR-4281".

[0179] The term "hsa-miR-6820-5p gene" or "hsa-miR-6820-5p" used herein includes the hsa-miR-6820-5p gene (miRBase Accession No. MIMAT0027540) described in SEQ ID NO: 132, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6820-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6820" (miRBase Accession No. MI0022665, SEQ ID NO: 330) having a hairpin-like structure is known as a precursor of "hsa-miR-6820-5p".

[0180] The term "hsa-miR-6795-5p gene" or "hsa-miR-6795-5p" used herein includes the hsa-miR-6795-5p gene (miRBase Accession No. MIMAT0027490) described in SEQ ID NO: 133, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6795-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6795" (miRBase Accession No. MI0022640, SEQ ID NO: 331) having a hairpin-like structure is known as a precursor of "hsa-miR-6795-5p".

[0181] The term "hsa-miR-6779-5p gene" or "hsa-miR-6779-5p" used herein includes the hsa-miR-6779-5p gene (miRBase Accession No. MIMAT0027458) described in SEQ ID NO: 134, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6779-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6779" (miRBase Accession No. MI0022624, SEQ ID NO: 332) having a hairpin-like structure is known as a precursor of "hsa-miR-6779-5p".

[0182] The term "hsa-miR-7109-5p gene" or "hsa-miR-7109-5p" used herein includes the hsa-miR-7109-5p gene (miRBase Accession No. MIMAT0028115) described in SEQ ID NO: 135, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-7109-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-7109" (miRBase Accession No. MI0022960, SEQ ID NO: 333) having a hairpin-like structure is known as a precursor of "hsa-miR-7109-5p".

[0183] The term "hsa-miR-6798-5p gene" or "hsa-miR-6798-5p" used herein includes the hsa-miR-6798-5p gene (miRBase Accession No. MIMAT0027496) described in SEQ ID NO: 136, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6798-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6798" (miRBase Accession No. MI0022643, SEQ ID NO: 334) having a hairpin-like structure is known as a precursor of "hsa-miR-6798-5p".

[0184] The term "hsa-miR-4648 gene" or "hsa-miR-4648" used herein includes the hsa-miR-4648 gene (miRBase Accession No. MIMAT0019710) described in SEQ ID NO: 137, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4648 gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4648" (miRBase Accession No. MI0017275, SEQ ID NO: 335) having a hairpin-like structure is known as a precursor of "hsa-miR-4648".

[0185] The term "hsa-miR-8059 gene" or "hsa-miR-8059" used herein includes the hsa-miR-8059 gene (miRBase Accession No. MIMAT0030986) described in SEQ ID NO: 138, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-8059 gene can be obtained by a method described in Wang HJ et al., 2013, Shock, Vol. 39, p. 480-487. Also, "hsa-mir-8059" (miRBase Accession No. MI0025895, SEQ ID NO: 336) having a hairpin-like structure is known as a precursor of "hsa-miR-8059".

[0186] The term "hsa-miR-6765-3p gene" or "hsa-miR-6765-3p" used herein includes the hsa-miR-6765-3p gene (miRBase Accession No. MIMAT0027431) described in SEQ ID NO: 139, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6765-3p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 292) having a hairpin-like structure is known as a precursor of "hsa-miR-6765-3p".

[0187] The term "hsa-miR-6132 gene" or "hsa-miR-6132" used herein includes the hsa-miR-6132 gene (miRBase Accession No. MIMAT0024616) described in SEQ ID NO: 140, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6132 gene can be obtained by a method described in Dannemann M et al., 2012, Genome Biol Evol, Vol. 4, p. 552-564. Also, "hsa-mir-6132" (miRBase Accession No. MI0021277, SEQ ID NO: 337) having a hairpin-like structure is known as a precursor of "hsa-miR-6132".

[0188] The term "hsa-miR-4492 gene" or "hsa-miR-4492" used herein includes the hsa-miR-4492 gene (miRBase Accession No. MIMAT0019027) described in SEQ ID NO: 141, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4492 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4492" (miRBase Accession No. MI0016854, SEQ ID NO: 338) having a hairpin-like structure is known as a precursor of "hsa-miR-4492".

[0189] The term "hsa-miR-7107-5p gene" or "hsa-miR-7107-5p" used herein includes the hsa-miR-7107-5p gene (miRBase Accession No. MIMAT0028111) described in SEQ ID NO: 142, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-7107-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-7107" (miRBase Accession No. MI0022958, SEQ ID NO: 339) having a hairpin-like structure is known as a precursor of "hsa-miR-7107-5p".

[0190] The term "hsa-miR-3195 gene" or "hsa-miR-3195" used herein includes the hsa-miR-3195 gene (miRBase Accession No. MIMAT0015079) described in SEQ ID NO: 143, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3195 gene can be obtained by a method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Also, "hsa-mir-3195" (miRBase Accession No. MI0014240, SEQ ID NO: 340) having a hairpin-like structure is known as a precursor of "hsa-miR-3195".

[0191]  The term "hsa-miR-3180 gene" or "hsa-miR-3180" used herein includes the hsa-miR-3180 gene (miRBase Accession No. MIMAT0018178) described in SEQ ID NO: 144, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3180 gene can be obtained by a method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Also, "hsa-mir-3180-4 and hsa-mir-3180-5" (miRBase Accession Nos. MI0016408 and MI0016409, SEQ ID NOs: 341 and 342) having a hairpin-like structure are known as precursors of "hsa-miR-3180".

[0192] The term "hsa-miR-296-3p gene" or "hsa-miR-296-3p" used herein includes the hsa-miR-296-3p gene (miRBase Accession No. MIMAT0004679) described in SEQ ID NO: 145, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-296-3p gene can be obtained by a method described in Houbaviy HB et al., 2003, Dev Cell, Vol. 5, p. 351-358. Also, "hsa-mir-296" (miRBase Accession No. MI0000747, SEQ ID NO: 343) having a hairpin-like structure is known as a precursor of "hsa-miR-296-3p".

[0193] The term "hsa-miR-564 gene" or "hsa-miR-564" used herein includes the hsa-miR-564 gene (miRBase Accession No. MIMAT0003228) described in SEQ ID NO: 146, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-564 gene can be obtained by a method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, Vol. 103, p. 3687-3692. Also, "hsa-mir-564" (miRBase Accession No. MI0003570, SEQ ID NO: 344) having a hairpin-like structure is known as a precursor of "hsa-miR-564".

[0194] The term "hsa-miR-1268a gene" or "hsa-miR-1268a" used herein includes the hsa-miR-1268a gene (miRBase Accession No. MIMAT0005922) described in SEQ ID NO: 147, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1268a gene can be obtained by a method described in Morin RD et al., 2008, Genome Res, Vol. 18, p. 610-621. Also, "hsa-mir-1268a" (miRBase Accession No. MI0006405, SEQ ID NO: 345) having a hairpin-like structure is known as a precursor of "hsa-miR-1268a".

[0195] The term "hsa-miR-6848-5p gene" or "hsa-miR-6848-5p" used herein includes the hsa-miR-6848-5p gene (miRBase Accession No. MIMAT0027596) described in SEQ ID NO: 148, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6848-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6848" (miRBase Accession No. MI0022694, SEQ ID NO: 346) having a hairpin-like structure is known as a precursor of "hsa-miR-6848-5p".

[0196] The term "hsa-miR-762 gene" or "hsa-miR-762" used herein includes the hsa-miR-762 gene (miRBase Accession No. MIMAT0010313) described in SEQ ID NO: 149, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-762 gene can be obtained by a method described in Berezikov E et al., 2006, Genome Res, Vol. 16, p. 1289-1298. Also, "hsa-mir-762" (miRBase Accession No. MI0003892, SEQ ID NO: 347) having a hairpin-like structure is known as a precursor of "hsa-miR-762".

[0197] The term "hsa-miR-2861 gene" or "hsa-miR-2861" used herein includes the hsa-miR-2861 gene (miRBase Accession No. MIMAT0013802) described in SEQ ID NO: 150, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-2861 gene can be obtained by a method described in Li H et al., 2009, J Clin Invest, Vol. 119, p. 3666-3677. Also, "hsa-mir-2861" (miRBase Accession No. MI0013006, SEQ ID NO: 348) having a hairpin-like structure is known as a precursor of "hsa-miR-2861".

[0198] The term "hsa-miR-1203 gene" or "hsa-miR-1203" used herein includes the hsa-miR-1203 gene (miRBase Accession No. MIMAT0005866) described in SEQ ID NO: 151, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1203 gene can be obtained by a method described in Marton S et al., 2008, Leukemia, Vol. 22, p. 330-338. Also, "hsa-mir-1203" (miRBase Accession No. MI0006335, SEQ ID NO: 349) having a hairpin-like structure is known as a precursor of "hsa-miR-1203".

[0199] The term "hsa-miR-1260b gene" or "hsa-miR-1260b" used herein includes the hsa-miR-1260b gene (miRBase Accession No. MIMAT0015041) described in SEQ ID NO: 152, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1260b gene can be obtained by a method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Also, "hsa-mir-1260b" (miRBase Accession No. MI0014197, SEQ ID NO: 350) having a hairpin-like structure is known as a precursor of "hsa-miR-1260b".

[0200] The term "hsa-miR-4476 gene" or "hsa-miR-4476" used herein includes the hsa-miR-4476 gene (miRBase Accession No. MIMAT0019003) described in SEQ ID NO: 153, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4476 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4476" (miRBase Accession No. MI0016828, SEQ ID NO: 351) having a hairpin-like structure is known as a precursor of "hsa-miR-4476".

[0201] The term "hsa-miR-6885-5p gene" or "hsa-miR-6885-5p" used herein includes the hsa-miR-6885-5p gene (miRBase Accession No. MIMAT0027670) described in SEQ ID NO: 154, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6885-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6885" (miRBase Accession No. MI0022732, SEQ ID NO: 352) having a hairpin-like structure is known as a precursor of "hsa-miR-6885-5p".

[0202] The term "hsa-miR-6769b-5p gene" or "hsa-miR-6769b-5p" used herein includes the hsa-miR-6769b-5p gene (miRBase Accession No. MIMAT0027620) described in SEQ ID NO: 155, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6769b-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6769b" (miRBase Accession No. MI0022706, SEQ ID NO: 353) having a hairpin-like structure is known as a precursor of "hsa-miR-6769b-5p".

[0203] The term "hsa-miR-23b-3p gene" or "hsa-miR-23b-3p" used herein includes the hsa-miR-23b-3p gene (miRBase Accession No. MIMAT0000418) described in SEQ ID NO: 156, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-23b-3p gene can be obtained by a method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p. 735-739. Also, "hsa-mir-23b" (miRBase Accession No. MI0000439, SEQ ID NO: 354) having a hairpin-like structure is known as a precursor of "hsa-miR-23b-3p".

[0204] The term "hsa-miR-1343-5p gene" or "hsa-miR-1343-5p" used herein includes the hsa-miR-1343-5p gene (miRBase Accession No. MIMAT0027038) described in SEQ ID NO: 157, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1343-5p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 202) having a hairpin-like structure is known as a precursor of "hsa-miR-1343-5p".

[0205] The term "hsa-miR-3621 gene" or "hsa-miR-3621" used herein includes the hsa-miR-3621 gene (miRBase Accession No. MIMAT0018002) described in SEQ ID NO: 158, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3621 gene can be obtained by a method described in Witten D et al., 2010, BMC Biol, Vol. 8, p. 58. Also, "hsa-mir-3621" (miRBase Accession No. MI0016012, SEQ ID NO: 355) having a hairpin-like structure is known as a precursor of "hsa-miR-3621".

[0206] The term "hsa-miR-4688 gene" or "hsa-miR-4688" used herein includes the hsa-miR-4688 gene (miRBase Accession No. MIMAT0019777) described in SEQ ID NO: 159, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4688 gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4688" (miRBase Accession No. MI0017321, SEQ ID NO: 356) having a hairpin-like structure is known as a precursor of "hsa-miR-4688".

[0207] The term "hsa-miR-4286 gene" or "hsa-miR-4286" used herein includes the hsa-miR-4286 gene (miRBase Accession No. MIMAT0016916) described in SEQ ID NO: 160, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4286 gene can be obtained by a method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Also, "hsa-mir-4286" (miRBase Accession No. MI0015894, SEQ ID NO: 357) having a hairpin-like structure is known as a precursor of "hsa-miR-4286".

[0208] The term "hsa-miR-4640-5p gene" or "hsa-miR-4640-5p" used herein includes the hsa-miR-4640-5p gene (miRBase Accession No. MIMAT0019699) described in SEQ ID NO: 161, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4640-5p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4640" (miRBase Accession No. MI0017267, SEQ ID NO: 358) having a hairpin-like structure is known as a precursor of "hsa-miR-4640-5p".

[0209] The term "hsa-miR-4739 gene" or "hsa-miR-4739" used herein includes the hsa-miR-4739 gene (miRBase Accession No. MIMAT0019868) described in SEQ ID NO: 162, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4739 gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4739" (miRBase Accession No. MI0017377, SEQ ID NO: 359) having a hairpin-like structure is known as a precursor of "hsa-miR-4739".

[0210] The term "hsa-miR-1260a gene" or "hsa-miR-1260a" used herein includes the hsa-miR-1260a gene (miRBase Accession No. MIMAT0005911) described in SEQ ID NO: 163, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1260a gene can be obtained by a method described in Morin RD et al., 2008, Genome Res, Vol. 18, p. 610-621. Also, "hsa-mir-1260a" (miRBase Accession No. MI0006394, SEQ ID NO: 360) having a hairpin-like structure is known as a precursor of "hsa-miR-1260a".

[0211] The term "hsa-miR-4276 gene" or "hsa-miR-4276" used herein includes the hsa-miR-4276 gene (miRBase Accession No. MIMAT0016904) described in SEQ ID NO: 164, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4276 gene can be obtained by a method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Also, "hsa-mir-4276" (miRBase Accession No. MI0015882, SEQ ID NO: 361) having a hairpin-like structure is known as a precursor of "hsa-miR-4276".

[0212] The term "hsa-miR-7106-5p gene" or "hsa-miR-7106-5p" used herein includes the hsa-miR-7106-5p gene (miRBase Accession No. MIMAT0028109) described in SEQ ID NO: 165, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-7106-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-7106" (miRBase Accession No. MI0022957, SEQ ID NO: 362) having a hairpin-like structure is known as a precursor of "hsa-miR-7106-5p".

[0213]  The term "hsa-miR-128-2-5p gene" or "hsa-miR-128-2-5p" used herein includes the hsa-miR-128-2-5p gene (miRBase Accession No. MIMAT0031095) described in SEQ ID NO: 166, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-128-2-5p gene can be obtained by a method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p. 735-739. Also, "hsa-mir-128-2" (miRBase Accession No. MI0000727, SEQ ID NO: 363) having a hairpin-like structure is known as a precursor of "hsa-miR-128-2-5p".

[0214] The term "hsa-miR-125a-3p gene" or "hsa-miR-125a-3p" used herein includes the hsa-miR-125a-3p gene (miRBase Accession No. MIMAT0004602) described in SEQ ID NO: 167, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-125a-3p gene can be obtained by a method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p. 735-739. Also, "hsa-mir-125a" (miRBase Accession No. MI0000469, SEQ ID NO: 364) having a hairpin-like structure is known as a precursor of "hsa-miR-125a-3p".

[0215] The term "hsa-miR-92a-2-5p gene" or "hsa-miR-92a-2-5p" used herein includes the hsa-miR-92a-2-5p gene (miRBase Accession No. MIMAT0004508) described in SEQ ID NO: 168, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-92a-2-5p gene can be obtained by a method described in Mourelatos Z et al., 2002, Genes Dev, Vol. 16, p. 720-728. Also, "hsa-mir-92a-2" (miRBase Accession No. MI0000094, SEQ ID NO: 365) having a hairpin-like structure is known as a precursor of "hsa-miR-92a-2-5p".

[0216] The term "hsa-miR-486-3p gene" or "hsa-miR-486-3p" used herein includes the hsa-miR-486-3p gene (miRBase Accession No. MIMAT0004762) described in SEQ ID NO: 169, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-486-3p gene can be obtained by a method described in Fu H et al., 2005, FEBS Lett, Vol. 579, p. 3849-3854. Also, "hsa-mir-486 and hsa-mir-486-2" (miRBase Accession Nos. MI0002470 and MI0023622, SEQ ID NOs: 366 and 367) having a hairpin-like structure are known as precursors of "hsa-miR-486-3p".

[0217] The term "hsa-miR-3196 gene" or "hsa-miR-3196" used herein includes the hsa-miR-3196 gene (miRBase Accession No. MIMAT0015080) described in SEQ ID NO: 170, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3196 gene can be obtained by a method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Also, "hsa-mir-3196" (miRBase Accession No. MI0014241, SEQ ID NO: 368) having a hairpin-like structure is known as a precursor of "hsa-miR-3196".

[0218] The term "hsa-miR-211-3p gene" or "hsa-miR-211-3p" used herein includes the hsa-miR-211-3p gene (miRBase Accession No. MIMAT0022694) described in SEQ ID NO: 171, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-211-3p gene can be obtained by a method described in Lim LP et al., 2003, Science, Vol. 299, p. 1540. Also, "hsa-mir-211" (miRBase Accession No. MI0000287, SEQ ID NO: 369) having a hairpin-like structure is known as a precursor of "hsa-miR-211-3p".

[0219] The term "hsa-miR-4271 gene" or "hsa-miR-4271" used herein includes the hsa-miR-4271 gene (miRBase Accession No. MIMAT0016901) described in SEQ ID NO: 172, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4271 gene can be obtained by a method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Also, "hsa-mir-4271" (miRBase Accession No. MI0015879, SEQ ID NO: 370) having a hairpin-like structure is known as a precursor of "hsa-miR-4271".

[0220] The term "hsa-miR-6851-5p gene" or "hsa-miR-6851-5p" used herein includes the hsa-miR-6851-5p gene (miRBase Accession No. MIMAT0027602) described in SEQ ID NO: 173, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6851-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6851" (miRBase Accession No. MI0022697, SEQ ID NO: 371) having a hairpin-like structure is known as a precursor of "hsa-miR-6851-5p".

[0221] The term "hsa-miR-149-3p gene" or "hsa-miR-149-3p" used herein includes the hsa-miR-149-3p gene (miRBase Accession No. MIMAT0004609) described in SEQ ID NO: 174, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-149-3p gene can be obtained by a method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p. 735-739. Also, "hsa-mir-149" (miRBase Accession No. MI0000478, SEQ ID NO: 372) having a hairpin-like structure is known as a precursor of "hsa-miR-149-3p".

[0222] The term "hsa-miR-4667-5p gene" or "hsa-miR-4667-5p" used herein includes the hsa-miR-4667-5p gene (miRBase Accession No. MIMAT0019743) described in SEQ ID NO: 175, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4667-5p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4667" (miRBase Accession No. MI0017297, SEQ ID NO: 373) having a hairpin-like structure is known as a precursor of "hsa-miR-4667-5p".

[0223] The term "hsa-miR-135a-3p gene" or "hsa-miR-135a-3p" used herein includes the hsa-miR-135a-3p gene (miRBase Accession No. MIMAT0004595) described in SEQ ID NO: 176, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-135a-3p gene can be obtained by a method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p. 735-739. Also, "hsa-mir-135a-1" (miRBase Accession No. MI0000452, SEQ ID NO: 374) having a hairpin-like structure is known as a precursor of "hsa-miR-135a-3p".

[0224] The term "hsa-miR-4486 gene" or "hsa-miR-4486" used herein includes the hsa-miR-4486 gene (miRBase Accession No. MIMAT0019020) described in SEQ ID NO: 177, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4486 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4486" (miRBase Accession No. MI0016847, SEQ ID NO: 375) having a hairpin-like structure is known as a precursor of "hsa-miR-4486".

[0225] The term "hsa-miR-4697-5p gene" or "hsa-miR-4697-5p" used herein includes the hsa-miR-4697-5p gene (miRBase Accession No. MIMAT0019791) described in SEQ ID NO: 178, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4697-5p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4697" (miRBase Accession No. MI0017330, SEQ ID NO: 376) having a hairpin-like structure is known as a precursor of "hsa-miR-4697-5p".

[0226] The term "hsa-miR-4725-3p gene" or "hsa-miR-4725-3p" used herein includes the hsa-miR-4725-3p gene (miRBase Accession No. MIMAT0019844) described in SEQ ID NO: 179, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4725-3p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4725" (miRBase Accession No. MI0017362, SEQ ID NO: 377) having a hairpin-like structure is known as a precursor of "hsa-miR-4725-3p".

[0227] The term "hsa-miR-6510-5p gene" or "hsa-miR-6510-5p" used herein includes the hsa-miR-6510-5p gene (miRBase Accession No. MIMAT0025476) described in SEQ ID NO: 180, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6510-5p gene can be obtained by a method described in Joyce CE et al., 2011, Hum Mol Genet, Vol. 20, p. 4025-4040. Also, "hsa-mir-6510" (miRBase Accession No. MI0022222, SEQ ID NO: 378) having a hairpin-like structure is known as a precursor of "hsa-miR-6510-5p".

[0228] The term "hsa-miR-5001-5p gene" or "hsa-miR-5001-5p" used herein includes the hsa-miR-5001-5p gene (miRBase Accession No. MIMAT0021021) described in SEQ ID NO: 181, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-5001-5p gene can be obtained by a method described in Hansen TB et al., 2011, RNA Biol, Vol. 8, p. 378-383. Also, "hsa-mir-5001" (miRBase Accession No. MI0017867, SEQ ID NO: 379) having a hairpin-like structure is known as a precursor of "hsa-miR-5001-5p".

[0229] The term "hsa-miR-4673 gene" or "hsa-miR-4673" used herein includes the hsa-miR-4673 gene (miRBase Accession No. MIMAT0019755) described in SEQ ID NO: 182, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4673 gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4673" (miRBase Accession No. MI0017304, SEQ ID NO: 380) having a hairpin-like structure is known as a precursor of "hsa-miR-4673".

[0230] The term "hsa-miR-4466 gene" or "hsa-miR-4466" used herein includes the hsa-miR-4466 gene (miRBase Accession No. MIMAT0018993) described in SEQ ID NO: 183, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4466 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4466" (miRBase Accession No. MI0016817, SEQ ID NO: 381) having a hairpin-like structure is known as a precursor of "hsa-miR-4466".

[0231] The term "hsa-miR-23a-3p gene" or "hsa-miR-23a-3p" used herein includes the hsa-miR-23a-3p gene (miRBase Accession No. MIMAT0000078) described in SEQ ID NO: 184, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-23a-3p gene can be obtained by a method described in Lagos-Quintana M et al., 2001, Science, Vol. 294, p. 853-858. Also, "hsa-mir-23a" (miRBase Accession No. MI0000079, SEQ ID NO: 382) having a hairpin-like structure is known as a precursor of "hsa-miR-23a-3p".

[0232] The term "hsa-miR-3656 gene" or "hsa-miR-3656" used herein includes the hsa-miR-3656 gene (miRBase Accession No. MIMAT0018076) described in SEQ ID NO: 185, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3656 gene can be obtained by a method described in Meiri E et al., 2010, Nucleic Acids Res, Vol. 38, p. 6234-6246. Also, "hsa-mir-3656" (miRBase Accession No. MI0016056, SEQ ID NO: 383) having a hairpin-like structure is known as a precursor of "hsa-miR-3656".

[0233] The term "hsa-miR-6782-5p gene" or "hsa-miR-6782-5p" used herein includes the hsa-miR-6782-5p gene (miRBase Accession No. MIMAT0027464) described in SEQ ID NO: 186, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6782-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6782" (miRBase Accession No. MI0022627, SEQ ID NO: 384) having a hairpin-like structure is known as a precursor of "hsa-miR-6782-5p".

[0234] The term "hsa-miR-4689 gene" or "hsa-miR-4689" used herein includes the hsa-miR-4689 gene (miRBase Accession No. MIMAT0019778) described in SEQ ID NO: 187, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4689 gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4689" (miRBase Accession No. MI0017322, SEQ ID NO: 385) having a hairpin-like structure is known as a precursor of "hsa-miR-4689".

[0235]  The term "hsa-miR-451a gene" or "hsa-miR-451a" used herein includes the hsa-miR-451a gene (miRBase Accession No. MIMAT0001631) described in SEQ ID NO: 188, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-451a gene can be obtained by a method described in Altuvia Y et al., 2005, Nucleic Acids Res, Vol. 33, p. 2697-2706. Also, "hsa-mir-451a" (miRBase Accession No. MI0001729, SEQ ID NO: 386) having a hairpin-like structure is known as a precursor of "hsa-miR-451a".

[0236] The term "hsa-miR-4446-3p gene" or "hsa-miR-4446-3p" used herein includes the hsa-miR-4446-3p gene (miRBase Accession No. MIMAT0018965) described in SEQ ID NO: 189, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4446-3p gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4446" (miRBase Accession No. MI0016789, SEQ ID NO: 387) having a hairpin-like structure is known as a precursor of "hsa-miR-4446-3p".

[0237] The term "hsa-miR-3180-3p gene" or "hsa-miR-3180-3p" used herein includes the hsa-miR-3180-3p gene (miRBase Accession No. MIMAT0015058) described in SEQ ID NO: 190, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3180-3p gene can be obtained by a method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Also, "hsa-mir-3180-1, hsa-mir-3180-2, and hsa-mir-3180-3" (miRBase Accession Nos. MI0014214, MI0014215, and MI0014217, SEQ ID NOs: 388, 389, and 390) having a hairpin-like structure are known as precursors of "hsa-miR-3180-3p".

[0238] The term "hsa-miR-642a-3p gene" or "hsa-miR-642a-3p" used herein includes the hsa-miR-642a-3p gene (miRBase Accession No. MIMAT0020924) described in SEQ ID NO: 191, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-642a-3p gene can be obtained by a method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, Vol. 103, p. 3687-3692. Also, "hsa-mir-642a" (miRBase Accession No. MI0003657, SEQ ID NO: 391) having a hairpin-like structure is known as a precursor of "hsa-miR-642a-3p".

[0239] The term "hsa-miR-6889-5p gene" or "hsa-miR-6889-5p" used herein includes the hsa-miR-6889-5p gene (miRBase Accession No. MIMAT0027678) described in SEQ ID NO: 192, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6889-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6889" (miRBase Accession No. MI0022736, SEQ ID NO: 392) having a hairpin-like structure is known as a precursor of "hsa-miR-6889-5p".

[0240] The term "hsa-miR-3178 gene" or "hsa-miR-3178" used herein includes the hsa-miR-3178 gene (miRBase Accession No. MIMAT0015055) described in SEQ ID NO: 193, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3178 gene can be obtained by a method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Also, "hsa-mir-3178" (miRBase Accession No. MI0014212, SEQ ID NO: 393) having a hairpin-like structure is known as a precursor of "hsa-miR-3178".

[0241] The term "hsa-miR-4665-5p gene" or "hsa-miR-4665-5p" used herein includes the hsa-miR-4665-5p gene (miRBase Accession No. MIMAT0019739) described in SEQ ID NO: 194, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4665-5p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4665" (miRBase Accession No. MI0017295, SEQ ID NO: 323) having a hairpin-like structure is known as a precursor of "hsa-miR-4665-5p".

[0242] The term "hsa-miR-6722-3p gene" or "hsa-miR-6722-3p" used herein includes the hsa-miR-6722-3p gene (miRBase Accession No. MIMAT0025854) described in SEQ ID NO: 195, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6722-3p gene can be obtained by a method described in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. Also, "hsa-mir-6722" (miRBase Accession No. MI0022557, SEQ ID NO: 394) having a hairpin-like structure is known as a precursor of "hsa-miR-6722-3p".

[0243] The term "hsa-miR-30c-1-3p gene" or "hsa-miR-30c-1-3p" used herein includes the hsa-miR-30c-1-3p gene (miRBase Accession No. MIMAT0004674) described in SEQ ID NO: 196, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-30c-1-3p gene can be obtained by a method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p. 735-739. Also, "hsa-mir-30c-1" (miRBase Accession No. MI0000736, SEQ ID NO: 395) having a hairpin-like structure is known as a precursor of "hsa-miR-30c-1-3p".

[0244] The term "hsa-miR-4507 gene" or "hsa-miR-4507" used herein includes the hsa-miR-4507 gene (miRBase Accession No. MIMAT0019044) described in SEQ ID NO: 197, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4507 gene can be obtained by a method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-mir-4507" (miRBase Accession No. MI0016871, SEQ ID NO: 396) having a hairpin-like structure is known as a precursor of "hsa-miR-4507".

[0245] The term "hsa-miR-3141 gene" or "hsa-miR-3141" used herein includes the hsa-miR-3141 gene (miRBase Accession No. MIMAT0015010) described in SEQ ID NO: 198, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-3141 gene can be obtained by a method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Also, "hsa-mir-3141" (miRBase Accession No. MI0014165, SEQ ID NO: 397) having a hairpin-like structure is known as a precursor of "hsa-miR-3141".

[0246] The term "hsa-miR-1199-5p gene" or "hsa-miR-1199-5p" used herein includes the hsa-miR-1199-5p gene (miRBase Accession No. MIMAT0031119) described in SEQ ID NO: 199, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-1199-5p gene can be obtained by a method described in Salvi A et al., 2013, Int J Oncol, Vol. 42, p. 391-402. Also, "hsa-mir-1199" (miRBase Accession No. MI0020340, SEQ ID NO: 398) having a hairpin-like structure is known as a precursor of "hsa-miR-1199-5p".

[0247] The term "hsa-miR-6794-5p gene" or "hsa-miR-6794-5p" used herein includes the hsa-miR-6794-5p gene (miRBase Accession No. MIMAT0027488) described in SEQ ID NO: 635, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6794-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6794" (miRBase Accession No. MI0022639, SEQ ID NO: 643) having a hairpin-like structure is known as a precursor of "hsa-miR-6794-5p".

[0248]  The term "hsa-miR-6774-5p gene" or "hsa-miR-6774-5p" used herein includes the hsa-miR-6774-5p gene (miRBase Accession No. MIMAT0027448) described in SEQ ID NO: 636, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6774-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645. Also, "hsa-mir-6774" (miRBase Accession No. MI0022619, SEQ ID NO: 644) having a hairpin-like structure is known as a precursor of "hsa-miR-6774-5p".

[0249] The term "hsa-miR-4707-3p gene" or "hsa-miR-4707-3p" used herein includes the hsa-miR-4707-3p gene (miRBase Accession No. MIMAT0019808) described in SEQ ID NO: 637, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4707-3p gene can be obtained by a method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-mir-4707" (miRBase Accession No. MI0017340, SEQ ID NO: 645) having a hairpin-like structure is known as a precursor of "hsa-miR-4707-3p".

[0250] The term "hsa-miR-4534 gene" or "hsa-miR-4534" used herein includes the hsa-miR-4534 gene (miRBase Accession No. MIMAT0019073) described in SEQ ID NO: 638, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4534 gene can be obtained by a method described in Jima DD et al., 2010, Blood., Vol. 116, e118-e127. Also, "hsa-mir-4534" (miRBase Accession No. MI0016901, SEQ ID NO: 646) having a hairpin-like structure is known as a precursor of "hsa-miR-4534".

[0251] The term "hsa-miR-4294 gene" or "hsa-miR-4294" used herein includes the hsa-miR-4294 gene (miRBase Accession No. MIMAT0016849) described in SEQ ID NO: 639, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-4294 gene can be obtained by a method described in Goff LA et al., 2009, PLoS One., Vol. 4, e7192. Also, "hsa-mir-4294" (miRBase Accession No. MI0015827, SEQ ID NO: 647) having a hairpin-like structure is known as a precursor of "hsa-miR-4294".

[0252] The term "hsa-miR-6850-5p gene" or "hsa-miR-6850-5p" used herein includes the hsa-miR-6850-5p gene (miRBase Accession No. MIMAT0027600) described in SEQ ID NO: 640, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6850-5p gene can be obtained by a method described in Ladewig E et al., 2012, Genome Res., Vol. 22, p. 1634-1645. Also, "hsa-mir-6850" (miRBase Accession No. MI0022696, SEQ ID NO: 648) having a hairpin-like structure is known as a precursor of "hsa-miR-6850-5p".

[0253] The term "hsa-miR-6089 gene" or "hsa-miR-6089" used herein includes the hsa-miR-6089 gene (miRBase Accession No. MIMAT0023714) described in SEQ ID NO: 641, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-6089 gene can be obtained by a method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, p. 2049-2057. Also, "hsa-mir-6089-1 and hsa-mir-6089-2" (miRBase Accession Nos. MI0020366 and MI0023563, SEQ ID NOs: 649 and 650) having a hairpin-like structure are known as precursors of "hsa-miR-6089".

[0254] The term "hsa-miR-671-5p gene" or "hsa-miR-671-5p" used herein includes the hsa-miR-671-5p gene (miRBase Accession No. MIMAT0003880) described in SEQ ID NO: 642, a homolog or an ortholog of a different organism species, and the like. The hsa-miR-671-5p gene can be obtained by a method described in Berezikov E et al., 2006, Genome Res, Vol. 16, p. 1289-1298. Also, "hsa-mir-671" (miRBase Accession No. MI0003760, SEQ ID NO: 651) having a hairpin-like structure is known as a precursor of "hsa-miR-671-5p".

[0255] A mature miRNA may become a variant due to the sequence cleaved shorter or longer by one to several flanking nucleotides or due to substitution of nucleotides when cleaved as the mature miRNA from its RNA precursor having a hairpin-like structure. This variant is called isomiR (Morin RD. et al., 2008, Genome Res., Vol. 18, p. 610-621). The miRBase Release 20 shows the nucleotide sequences represented by SEQ ID NOs: 1 to 199 and 635 to 642 as well as a large number of the nucleotide sequence variants and fragments represented by SEQ ID NOs: 399 to 634 and 652 to 657, called isomiRs. These variants can also be obtained as miRNAs having a nucleotide sequence represented by any of SEQ ID NOs: 1 to 199 and 635 to 642.

[0256] Specifically, among the variants of polynucleotides consisting of the nucleotide sequence represented by any of SEQ ID NOs: 3, 4, 11, 13, 14, 18, 20, 21, 26, 29, 35, 36, 39, 41, 42, 45, 46, 47, 48, 49, 51, 53, 54, 55, 56, 57, 58, 59, 60, 62, 65, 66, 67, 68, 71, 72, 73, 74, 75, 76, 78, 82, 83, 88, 90, 91, 92, 94, 95, 98, 99, 101, 102, 103, 104, 106, 107, 108, 109, 110, 113, 116, 117, 118, 120, 121, 122, 123, 125, 128, 129, 130, 131, 137, 140, 141, 143, 144, 145, 146, 147, 150, 152, 153, 156, 159, 160, 161, 162, 163, 166, 167, 168, 169, 170, 171, 172, 174, 175, 176, 177, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 193, 194, 196, 197, 198, 637, 641 and 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t according to the present invention, examples of the longest variants registered in the miRBase Release 20 include polynucleotides represented by SEQ ID NOs: 399, 401, 403, 405, 407, 409, 411, 413, 415, 417, 419, 421, 423, 425, 427, 429, 431, 433, 435, 437, 439, 441, 443, 445, 447, 449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 471, 473, 475, 477, 479, 481, 483, 485, 487, 489, 491, 493, 495, 497, 499, 501, 503, 505, 507, 509, 511, 513, 515, 517, 519, 521, 523, 525, 527, 529, 531, 533, 535, 537, 539, 541, 543, 545, 547, 549, 551, 553, 555, 557, 559, 561, 563, 565, 567, 569, 571, 573, 575, 577, 579, 581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619, 621, 623, 625, 627, 629, 631, 633, 652, 654 and 656, respectively.

[0257] Also, among the variants of polynucleotides consisting of a nucleotide sequence represented by any of SEQ ID NOs: 3, 4, 11, 13, 14, 18, 20, 21, 26, 29, 35, 36, 39, 41, 42, 45, 46, 47, 48, 49, 51, 53, 54, 55, 56, 57, 58, 59, 60, 62, 65, 66, 67, 68, 71, 72, 73, 74, 75, 76, 78, 82, 83, 88, 90, 91, 92, 94, 95, 98, 99, 101, 102, 103, 104, 106, 107, 108, 109, 110, 113, 116, 117, 118, 120, 121, 122, 123, 125, 128, 129, 130, 131, 137, 140, 141, 143, 144, 145, 146, 147, 150, 152, 153, 156, 159, 160, 161, 162, 163, 166, 167, 168, 169, 170, 171, 172, 174, 175, 176, 177, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 193, 194, 196, 197, 198, 637, 641 and 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t according to the present invention, examples of the shortest variants registered in the miRBase Release 20 include polynucleotides having sequences represented by SEQ ID NOs: 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456, 458, 460, 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, 566, 568, 570, 572, 574, 576, 578, 580, 582, 584, 586, 588, 590, 592, 594, 596, 598, 600, 602, 604, 606, 608, 610, 612, 614, 616, 618, 620, 622, 624, 626, 628, 630, 632, 634, 653, 655 and 657, respectively. In addition to these variants and fragments, examples thereof include a large number of isomiR polynucleotides of SEQ ID NOs: 1 to 199 and 635 to 642 registered in the miRBase. Examples of the polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 1 to 199 and 635 to 642 include a polynucleotide represented by any of SEQ ID NOs: 200 to 398 and 643 to 651, which are their respective precursors.

[0258] The terms and miRBase Accession Nos. (registration numbers) of the genes represented by SEQ ID NOs: 1 to 657 are shown in Table 1.

[0259] The term "capable of specifically binding" used herein means that the nucleic acid probe or the primer used in the present invention binds to a particular target nucleic acid and cannot substantially bind to other nucleic acids.
[Table 1]
SEQ ID NO:Gene namemiRBase registration No.
1 hsa-miR-4257 MIMAT0016878
2 hsa-miR-6726-5p MIMAT0027353
3 hsa-miR-1343-3p MIMAT0019776
4 hsa-miR-1247-3p MIMAT0022721
5 hsa-miR-6787-5p MIMAT0027474
6 hsa-miR-6875-5p MIMAT0027650
7 hsa-miR-1225-3p MIMAT0005573
8 hsa-miR-8063 MIMAT0030990
9 hsa-miR-6781-5p MIMAT0027462
10 hsa-miR-4746-3p MIMAT0019881
11 hsa-miR-1908-5p MIMAT0007881
12 hsa-miR-6756-5p MIMAT0027412
13 hsa-miR-204-3p MIMAT0022693
14 hsa-miR-4651 MIMAT0019715
15 hsa-miR-6757-5p MIMAT0027414
16 hsa-miR-6825-5p MIMAT0027550
17 hsa-miR-7108-5p MIMAT0028113
18 hsa-miR-4792 MIMAT0019964
19 hsa-miR-7641 MIMAT0029782
20 hsa-miR-3188 MIMAT0015070
21 hsa-miR-3131 MIMAT0014996
22 hsa-miR-6780b-5p MIMAT0027572
23 hsa-miR-8069 MIMAT0030996
24 hsa-miR-6840-3p MIMAT0027583
25 hsa-miR-8072 MIMAT0030999
26 hsa-miR-1233-5p MIMAT0022943
27 hsa-miR-6887-5p MIMAT0027674
28 hsa-miR-1231 MIMAT0005586
29 hsa-miR-5572 MIMAT0022260
30 hsa-miR-6738-5p MIMAT0027377
31 hsa-miR-6784-5p MIMAT0027468
32 hsa-miR-6791-5p MIMAT0027482
33 hsa-miR-6749-5p MIMAT0027398
34 hsa-miR-6741-5p MIMAT0027383
35 hsa-miR-128-1-5p MIMAT0026477
36 hsa-miR-4419b MIMAT0019034
37 hsa-miR-6746-5p MIMAT0027392
38 hsa-miR-3184-5p MIMAT0015064
39 hsa-miR-3679-5p MIMAT0018104
40 hsa-miR-7110-5p MIMAT0028117
41 hsa-miR-4516 MIMAT0019053
42 hsa-miR-6717-5p MIMAT0025846
43 hsa-miR-6826-5p MIMAT0027552
44 hsa-miR-4433b-3p MIMAT0030414
45 hsa-miR-3679-3p MIMAT0018105
46 hsa-miR-3135b MIMAT0018985
47 hsa-miR-3622a-5p MIMAT0018003
48 hsa-miR-711 MIMAT0012734
49 hsa-miR-4467 MIMAT0018994
50 hsa-miR-6857-5p MIMAT0027614
51 hsa-miR-6515-3p MIMAT0025487
52 hsa-miR-1225-5p MIMAT0005572
53 hsa-miR-187-5p MIMAT0004561
54 hsa-miR-3185 MIMAT0015065
55 hsa-miR-642b-3p MIMAT0018444
56 hsa-miR-1249 MIMAT0005901
57 hsa-miR-744-5p MIMAT0004945
58 hsa-miR-4442 MIMAT0018960
59 hsa-miR-1228-3p MIMAT0005583
60 hsa-miR-939-5p MIMAT0004982
61 hsa-miR-6845-5p MIMAT0027590
62 hsa-miR-887-3p MIMAT0004951
63 hsa-miR-7845-5p MIMAT0030420
64 hsa-miR-6729-5p MIMAT0027359
65 hsa-miR-4632-5p MIMAT0022977
66 hsa-miR-615-5p MIMAT0004804
67 hsa-miR-6724-5p MIMAT0025856
68 hsa-miR-4728-5p MIMAT0019849
69 hsa-miR-6732-5p MIMAT0027365
70 hsa-miR-6816-5p MIMAT0027532
71 hsa-miR-4695-5p MIMAT0019788
72 hsa-miR-6088 MIMAT0023713
73 hsa-miR-7975 MIMAT0031178
74 hsa-miR-3197 MIMAT0015082
75 hsa-miR-6125 MIMAT0024598
76 hsa-miR-4433-3p MIMAT0018949
77 hsa-miR-6727-5p MIMAT0027355
78 hsa-miR-4706 MIMAT0019806
79 hsa-miR-7847-3p MIMAT0030422
80 hsa-miR-6805-3p MIMAT0027511
81 hsa-miR-6766-3p MIMAT0027433
82 hsa-miR-1913 MIMAT0007888
83 hsa-miR-4649-5p MIMAT0019711
84 hsa-miR-602 MIMAT0003270
85 hsa-miR-3663-3p MIMAT0018085
86 hsa-miR-6893-5p MIMAT0027686
87 hsa-miR-6861-5p MIMAT0027623
88 hsa-miR-4449 MIMAT0018968
89 hsa-miR-6842-5p MIMAT0027586
90 hsa-miR-4454 MIMAT0018976
91 hsa-miR-5195-3p MIMAT0021127
92 hsa-miR-663b MIMAT0005867
93 hsa-miR-6765-5p MIMAT0027430
94 hsa-miR-4513 MIMAT0019050
95 hsa-miR-614 MIMAT0003282
96 hsa-miR-6785-5p MIMAT0027470
97 hsa-miR-6777-5p MIMAT0027454
98 hsa-miR-940 MIMAT0004983
99 hsa-miR-4741 MIMAT0019871
100 hsa-miR-6870-5p MIMAT0027640
101 hsa-miR-6131 MIMAT0024615
102 hsa-miR-150-3p MIMAT0004610
103 hsa-miR-4707-5p MIMAT0019807
104 hsa-miR-1915-3p MIMAT0007892
105 hsa-miR-3937 MIMAT0018352
106 hsa-miR-937-5p MIMAT0022938
107 hsa-miR-4443 MIMAT0018961
108 hsa-miR-1914-3p MIMAT0007890
109 hsa-miR-3620-5p MIMAT0022967
110 hsa-miR-1268b MIMAT0018925
111 hsa-miR-1227-5p MIMAT0022941
112 hsa-miR-6880-5p MIMAT0027660
113 hsa-miR-4417 MIMAT0018929
114 hsa-miR-6802-5p MIMAT0027504
115 hsa-miR-6769a-5p MIMAT0027438
116 hsa-miR-663a MIMAT0003326
117 hsa-miR-6721-5p MIMAT0025852
118 hsa-miR-4532 MIMAT0019071
119 hsa-miR-7977 MIMAT0031180
120 hsa-miR-92b-5p MIMAT0004792
121 hsa-miR-371a-5p MIMAT0004687
122 hsa-miR-6126 MIMAT0024599
123 hsa-miR-4734 MIMAT0019859
124 hsa-miR-4665-3p MIMAT0019740
125 hsa-miR-423-5p MIMAT0004748
126 hsa-miR-1469 MIMAT0007347
127 hsa-miR-4675 MIMAT0019757
128 hsa-miR-1915-5p MIMAT0007891
129 hsa-miR-6716-5p MIMAT0025844
130 hsa-miR-718 MIMAT0012735
131 hsa-miR-4281 MIMAT0016907
132 hsa-miR-6820-5p MIMAT0027540
133 hsa-miR-6795-5p MIMAT0027490
134 hsa-miR-6779-5p MIMAT0027458
135 hsa-miR-7109-5p MIMAT0028115
136 hsa-miR-6798-5p MIMAT0027496
137 hsa-miR-4648 MIMAT0019710
138 hsa-miR-8059 MIMAT0030986
139 hsa-miR-6765-3p MIMAT0027431
140 hsa-miR-6132 MIMAT0024616
141 hsa-miR-4492 MIMAT0019027
142 hsa-miR-7107-5p MIMAT0028111
143 hsa-miR-3195 MIMAT0015079
144 hsa-miR-3180 MIMAT0018178
145 hsa-miR-296-3p MIMAT0004679
146 hsa-miR-564 MIMAT0003228
147 hsa-miR-1268a MIMAT0005922
148 hsa-miR-6848-5p MIMAT0027596
149 hsa-miR-762 MIMAT0010313
150 hsa-miR-2861 MIMAT0013802
151 hsa-miR-1203 MIMAT0005866
152 hsa-miR-1260b MIMAT0015041
153 hsa-miR-4476 MIMAT0019003
154 hsa-miR-6885-5p MIMAT0027670
155 hsa-miR-6769b-5p MIMAT0027620
156 hsa-miR-23b-3p MIMAT0000418
157 hsa-miR-1343-5p MIMAT0027038
158 hsa-miR-3621 MIMAT0018002
159 hsa-miR-4688 MIMAT0019777
160 hsa-miR-4286 MIMAT0016916
161 hsa-miR-4640-5p MIMAT0019699
162 hsa-miR-4739 MIMAT0019868
163 hsa-miR-1260a MIMAT0005911
164 hsa-miR-4276 MIMAT0016904
165 hsa-miR-7106-5p MIMAT0028109
166 hsa-miR-128-2-5p MIMAT0031095
167 hsa-miR-125a-3p MIMAT0004602
168 hsa-miR-92a-2-5p MIMAT0004508
169 hsa-miR-486-3p MIMAT0004762
170 hsa-miR-3196 MIMAT0015080
171 hsa-miR-211-3p MIMAT0022694
172 hsa-miR-4271 MIMAT0016901
173 hsa-miR-6851-5p MIMAT0027602
174 hsa-miR-149-3p MIMAT0004609
175 hsa-miR-4667-5p MIMAT0019743
176 hsa-miR-135a-3p MIMAT0004595
177 hsa-miR-4486 MIMAT0019020
178 hsa-miR-4697-5p MIMAT0019791
179 hsa-miR-4725-3p MIMAT0019844
180 hsa-miR-6510-5p MIMAT0025476
181 hsa-miR-5001-5p MIMAT0021021
182 hsa-miR-4673 MIMAT0019755
183 hsa-miR-4466 MIMAT0018993
184 hsa-miR-23a-3p MIMAT0000078
185 hsa-miR-3656 MIMAT0018076
186 hsa-miR-6782-5p MIMAT0027464
187 hsa-miR-4689 MIMAT0019778
188 hsa-miR-451a MIMAT0001631
189 hsa-miR-4446-3p MIMAT0018965
190 hsa-miR-3180-3p MIMAT0015058
191 hsa-miR-642a-3p MIMAT0020924
192 hsa-miR-6889-5p MIMAT0027678
193 hsa-miR-3178 MIMAT0015055
194 hsa-miR-4665-5p MIMAT0019739
195 hsa-miR-6722-3p MIMAT0025854
196 hsa-miR-30c-1-3p MIMAT0004674
197 hsa-miR-4507 MIMAT0019044
198 hsa-miR-3141 MIMAT0015010
199 hsa-miR-1199-5p MIMAT0031119
200 hsa-mir-4257 MI0015856
201 hsa-mir-6726 MI0022571
202 hsa-mir-1343 MI0017320
203 hsa-mir-1247 MI0006382
204 hsa-mir-6787 MI0022632
205 hsa-mir-6875 MI0022722
206 hsa-mir-1225 MI0006311
207 hsa-mir-8063 MI0025899
208 hsa-mir-6781 MI0022626
209 hsa-mir-4746 MI0017385
210 hsa-mir-1908 MI0008329
211 hsa-mir-6756 MI0022601
212 hsa-mir-204 MI0000284
213 hsa-mir-4651 MI0017279
214 hsa-mir-6757 MI0022602
215 hsa-mir-6825 MI0022670
216 hsa-mir-7108 MI0022959
217 hsa-mir-4792 MI0017439
218 hsa-mir-7641-1 MI0024975
219 hsa-mir-7641-2 MI0024976
220 hsa-mir-3188 MI0014232
221 hsa-mir-3131 MI0014151
222 hsa-mir-6780b MI0022681
223 hsa-mir-8069 MI0025905
224 hsa-mir-6840 MI0022686
225 hsa-mir-8072 MI0025908
226 hsa-mir-1233-1 MI0006323
227 hsa-mir-1233-2 MI0015973
228 hsa-mir-6887 MI0022734
229 hsa-mir-1231 MI0006321
230 hsa-mir-5572 MI0019117
231 hsa-mir-6738 MI0022583
232 hsa-mir-6784 MI0022629
233 hsa-mir-6791 MI0022636
234 hsa-mir-6749 MI0022594
235 hsa-mir-6741 MI0022586
236 hsa-mir-128-1 MI0000447
237 hsa-mir-4419b MI0016861
238 hsa-mir-6746 MI0022591
239 hsa-mir-3184 MI0014226
240 hsa-mir-3679 MI0016080
241 hsa-mir-7110 MI0022961
242 hsa-mir-4516 MI0016882
243 hsa-mir-6717 MI0022551
244 hsa-mir-6826 MI0022671
245 hsa-mir-4433b MI0025511
246 hsa-mir-3135b MI0016809
247 hsa-mir-3622a MI0016013
248 hsa-mir-711 MI0012488
249 hsa-mir-4467 MI0016818
250 hsa-mir-6857 MI0022703
251 hsa-mir-6515 MI0022227
252 hsa-mir-187 MI0000274
253 hsa-mir-3185 MI0014227
254 hsa-mir-642b MI0016685
255 hsa-mir-1249 MI0006384
256 hsa-mir-744 MI0005559
257 hsa-mir-4442 MI0016785
258 hsa-mir-1228 MI0006318
259 hsa-mir-939 MI0005761
260 hsa-mir-6845 MI0022691
261 hsa-mir-887 MI0005562
262 hsa-mir-7845 MI0025515
263 hsa-mir-6729 MI0022574
264 hsa-mir-4632 MI0017259
265 hsa-mir-615 MI0003628
266 hsa-mir-6724 MI0022559
267 hsa-mir-4728 MI0017365
268 hsa-mir-6732 MI0022577
269 hsa-mir-6816 MI0022661
270 hsa-mir-4695 MI0017328
271 hsa-mir-6088 MI0020365
272 hsa-mir-7975 MI0025751
273 hsa-mir-3197 MI0014245
274 hsa-mir-6125 MI0021259
275 hsa-mir-4433 MI0016773
276 hsa-mir-6727 MI0022572
277 hsa-mir-4706 MI0017339
278 hsa-mir-7847 MI0025517
279 hsa-mir-6805 MI0022650
280 hsa-mir-6766 MI0022611
281 hsa-mir-1913 MI0008334
282 hsa-mir-4649 MI0017276
283 hsa-mir-602 MI0003615
284 hsa-mir-3663 MI0016064
285 hsa-mir-6893 MI0022740
286 hsa-mir-6861 MI0022708
287 hsa-mir-4449 MI0016792
288 hsa-mir-6842 MI0022688
289 hsa-mir-4454 MI0016800
290 hsa-mir-5195 MI0018174
291 hsa-mir-663b MI0006336
292 hsa-mir-6765 MI0022610
293 hsa-mir-4513 MI0016879
294 hsa-mir-614 MI0003627
295 hsa-mir-6785 MI0022630
296 hsa-mir-6777 MI0022622
297 hsa-mir-940 MI0005762
298 hsa-mir-4741 MI0017379
299 hsa-mir-6870 MI0022717
300 hsa-mir-6131 MI0021276
301 hsa-mir-150 MI0000479
302 hsa-mir-4707 MI0017340
303 hsa-mir-1915 MI0008336
304 hsa-mir-3937 MI0016593
305 hsa-mir-937 MI0005759
306 hsa-mir-4443 MI0016786
307 hsa-mir-1914 MI0008335
308 hsa-mir-3620 MI0016011
309 hsa-mir-1268b MI0016748
310 hsa-mir-1227 MI0006316
311 hsa-mir-6880 MI0022727
312 hsa-mir-4417 MI0016753
313 hsa-mir-6802 MI0022647
314 hsa-mir-6769a MI0022614
315 hsa-mir-663a MI0003672
316 hsa-mir-6721 MI0022556
317 hsa-mir-4532 MI0016899
318 hsa-mir-7977 MI0025753
319 hsa-mir-92b MI0003560
320 hsa-mir-371a MI0000779
321 hsa-mir-6126 MI0021260
322 hsa-mir-4734 MI0017371
323 hsa-mir-4665 MI0017295
324 hsa-mir-423 MI0001445
325 hsa-mir-1469 MI0007074
326 hsa-mir-4675 MI0017306
327 hsa-mir-6716 MI0022550
328 hsa-mir-718 M10012489
329 hsa-mir-4281 MI0015885
330 hsa-mir-6820 MI0022665
331 hsa-mir-6795 MI0022640
332 hsa-mir-6779 MI0022624
333 hsa-mir-7109 MI0022960
334 hsa-mir-6798 MI0022643
335 hsa-mir-4648 MI0017275
336 hsa-mir-8059 MI0025895
337 hsa-mir-6132 MI0021277
338 hsa-mir-4492 MI0016854
339 hsa-mir-7107 MI0022958
340 hsa-mir-3195 MI0014240
341 hsa-mir-3180-4 M10016408
342 hsa-mir-3180-5 MI0016409
343 hsa-mir-296 MI0000747
344 hsa-mir-564 MI0003570
345 hsa-mir-1268a MI0006405
346 hsa-mir-6848 MI0022694
347 hsa-mir-762 MI0003892
348 hsa-mir-2861 MI0013006
349 hsa-mir-1203 MI0006335
350 hsa-mir-1260b MI0014197
351 hsa-mir-4476 MI0016828
352 hsa-mir-6885 MI0022732
353 hsa-mir-6769b MI0022706
354 hsa-mir-23b MI0000439
355 hsa-mir-3621 MI0016012
356 hsa-mir-4688 MI0017321
357 hsa-mir-4286 MI0015894
358 hsa-mir-4640 MI0017267
359 hsa-mir-4739 MI0017377
360 hsa-mir-1260a MI0006394
361 hsa-mir-4276 MI0015882
362 hsa-mir-7106 MI0022957
363 hsa-mir-128-2 MI0000727
364 hsa-mir-125a MI0000469
365 hsa-mir-92a-2 MI0000094
366 hsa-mir-486 MI0002470
367 hsa-mir-486-2 MI0023622
368 hsa-mir-3196 MI0014241
369 hsa-mir-211 MI0000287
370 hsa-mir-4271 MI0015879
371 hsa-mir-6851 MI0022697
372 hsa-mir-149 MI0000478
373 hsa-mir-4667 MI0017297
374 hsa-mir-135a-1 MI0000452
375 hsa-mir-4486 MI0016847
376 hsa-mir-4697 MI0017330
377 hsa-mir-4725 MI0017362
378 hsa-mir-6510 MI0022222
379 hsa-mir-5001 MI0017867
380 hsa-mir-4673 MI0017304
381 hsa-mir-4466 MI0016817
382 hsa-mir-23a MI0000079
383 hsa-mir-3656 MI0016056
384 hsa-mir-6782 MI0022627
385 hsa-mir-4689 MI0017322
386 hsa-mir-451a MI0001729
387 hsa-mir-4446 MI0016789
388 hsa-mir-3180-1 MI0014214
389 hsa-mir-3180-2 MI0014215
390 hsa-mir-3180-3 MI0014217
391 hsa-mir-642a MI0003657
392 hsa-mir-6889 MI0022736
393 hsa-mir-3178 MI0014212
394 hsa-mir-6722 MI0022557
395 hsa-mir-30c-1 MI0000736
396 hsa-mir-4507 MI0016871
397 hsa-mir-3141 MI0014165
398 hsa-mir-1199 MI0020340
399 isomiR example 1 of SEQ ID NO: 3 -
400 isomiR example 2 of SEQ ID NO: 3 -
401 isomiR example 1 of SEQ ID NO: 4 -
402 isomiR example 2 of SEQ ID NO: 4 -
403 isomiR example 1 of SEQ ID NO: 11 -
404 isomiR example 2 of SEQ ID NO: 11 -
405 isomiR example 1 of SEQ ID NO: 13 -
406 isomiR example 2 of SEQ ID NO: 13 -
407 isomiR example 1 of SEQ ID NO: 14 -
408 isomiR example 2 of SEQ ID NO: 14 -
409 isomiR example 1 of SEQ ID NO: 18 -
410 isomiR example 2 of SEQ ID NO: 18 -
411 isomiR example 1 of SEQ ID NO: 20 -
412 isomiR example 2 of SEQ ID NO: 20 -
413 isomiR example 1 of SEQ ID NO: 21 -
414 isomiR example 2 of SEQ ID NO: 21 -
415 isomiR example 1 of SEQ ID NO: 26 -
416 isomiR example 2 of SEQ ID NO: 26 -
417 isomiR example 1 of SEQ ID NO: 29 -
418 isomiR example 2 of SEQ ID NO: 29 -
419 isomiR example 1 of SEQ ID NO: 35 -
420 isomiR example 2 of SEQ ID NO: 35 -
421 isomiR example 1 of SEQ ID NO: 36 -
422 isomiR example 2 of SEQ ID NO: 36 -
423 isomiR example 1 of SEQ ID NO: 39 -
424 isomiR example 2 of SEQ ID NO: 39 -
425 isomiR example 1 of SEQ ID NO: 41 -
426 isomiR example 2 of SEQ ID NO: 41 -
427 isomiR example 1 of SEQ ID NO: 42 -
428 isomiR example 2 of SEQ ID NO: 42 -
429 isomiR example 1 of SEQ ID NO: 45 -
430 isomiR example 2 of SEQ ID NO: 45 -
431 isomiR example 1 of SEQ ID NO: 46 -
432 isomiR example 2 of SEQ ID NO: 46 -
433 isomiR example 1 of SEQ ID NO: 47 -
434 isomiR example 2 of SEQ ID NO: 47 -
435 isomiR example 1 of SEQ ID NO: 48 -
436 isomiR example 2 of SEQ ID NO: 48 -
437 isomiR example 1 of SEQ ID NO: 49 -
438 isomiR example 2 of SEQ ID NO: 49 -
439 isomiR example 1 of SEQ ID NO: 51 -
440 isomiR example 2 of SEQ ID NO: 51 -
441 isomiR example 1 of SEQ ID NO: 53 -
442 isomiR example 2 of SEQ ID NO: 53 -
443 isomiR example 1 of SEQ ID NO: 54 -
444 isomiR example 2 of SEQ ID NO: 54 -
445 isomiR example 1 of SEQ ID NO: 55 -
446 isomiR example 2 of SEQ ID NO: 55 -
447 isomiR example 1 of SEQ ID NO: 56 -
448 isomiR example 2 of SEQ ID NO: 56 -
449 isomiR example 1 of SEQ ID NO: 57 -
450 isomiR example 2 of SEQ ID NO: 57 -
451 isomiR example 1 of SEQ ID NO: 58 -
452 isomiR example 2 of SEQ ID NO: 58 -
453 isomiR example 1 of SEQ ID NO: 59 -
454 isomiR example 2 of SEQ ID NO: 59 -
455 isomiR example 1 of SEQ ID NO: 60 -
456 isomiR example 2 of SEQ ID NO: 60 -
457 isomiR example 1 of SEQ ID NO: 62 -
458 isomiR example 2 of SEQ ID NO: 62 -
459 isomiR example 1 of SEQ ID NO: 65 -
460 isomiR example 2 of SEQ ID NO: 65 -
461 isomiR example 1 of SEQ ID NO: 66 -
462 isomiR example 2 of SEQ ID NO: 66 -
463 isomiR example 1 of SEQ ID NO: 67 -
464 isomiR example 2 of SEQ ID NO: 67 -
465 isomiR example 1 of SEQ ID NO: 68 -
466 isomiR example 2 of SEQ ID NO: 68 -
467 isomiR example 1 of SEQ ID NO: 71 -
468 isomiR example 2 of SEQ ID NO: 71 -
469 isomiR example 1 of SEQ ID NO: 72 -
470 isomiR example 2 of SEQ ID NO: 72 -
471 isomiR example 1 of SEQ ID NO: 73 -
472 isomiR example 2 of SEQ ID NO: 73 -
473 isomiR example 1 of SEQ ID NO: 74 -
474 isomiR example 2 of SEQ ID NO: 74 -
475 isomiR example 1 of SEQ ID NO: 75 -
476 isomiR example 2 of SEQ ID NO: 75 -
477 isomiR example 1 of SEQ ID NO: 76 -
478 isomiR example 2 of SEQ ID NO: 76 -
479 isomiR example 1 of SEQ ID NO: 78 -
480 isomiR example 2 of SEQ ID NO: 78 -
481 isomiR example 1 of SEQ ID NO: 82 -
482 isomiR example 2 of SEQ ID NO: 82 -
483 isomiR example 1 of SEQ ID NO: 83 -
484 isomiR example 2 of SEQ ID NO: 83 -
485 isomiR example 1 of SEQ ID NO: 88 -
486 isomiR example 2 of SEQ ID NO: 88 -
487 isomiR example 1 of SEQ ID NO: 90 -
488 isomiR example 2 of SEQ ID NO: 90 -
489 isomiR example 1 of SEQ ID NO: 91 -
490 isomiR example 2 of SEQ ID NO: 91 -
491 isomiR example 1 of SEQ ID NO: 92 -
492 isomiR example 2 of SEQ ID NO: 92 -
493 isomiR example 1 of SEQ ID NO: 94 -
494 isomiR example 2 of SEQ ID NO: 94 -
495 isomiR example 1 of SEQ ID NO: 95 -
496 isomiR example 2 of SEQ ID NO: 95 -
497 isomiR example 1 of SEQ ID NO: 98 -
498 isomiR example 2 of SEQ ID NO: 98 -
499 isomiR example 1 of SEQ ID NO: 99 -
500 isomiR example 2 of SEQ ID NO: 99 -
501 isomiR example 1 of SEQ ID NO: 101 -
502 isomiR example 2 of SEQ ID NO: 101 -
503 isomiR example 1 of SEQ ID NO: 102 -
504 isomiR example 2 of SEQ ID NO: 102 -
505 isomiR example 1 of SEQ ID NO: 103 -
506 isomiR example 2 of SEQ ID NO: 103 -
507 isomiR example 1 of SEQ ID NO: 104 -
508 isomiR example 2 of SEQ ID NO: 104 -
509 isomiR example 1 of SEQ ID NO: 106 -
510 isomiR example 2 of SEQ ID NO: 106 -
511 isomiR example 1 of SEQ ID NO: 107 -
512 isomiR example 2 of SEQ ID NO: 107 -
513 isomiR example 1 of SEQ ID NO: 108 -
514 isomiR example 2 of SEQ ID NO: 108 -
515 isomiR example 1 of SEQ ID NO: 109 -
516 isomiR example 2 of SEQ ID NO: 109 -
517 isomiR example 1 of SEQ ID NO: 110 -
518 isomiR example 2 of SEQ ID NO: 110 -
519 isomiR example 1 of SEQ ID NO: 113 -
520 isomiR example 2 of SEQ ID NO: 113 -
521 isomiR example 1 of SEQ ID NO: 116 -
522 isomiR example 2 of SEQ ID NO: 116 -
523 isomiR example 1 of SEQ ID NO: 117 -
524 isomiR example 2 of SEQ ID NO: 117 -
525 isomiR example 1 of SEQ ID NO: 118 -
526 isomiR example 2 of SEQ ID NO: 118 -
527 isomiR example 1 of SEQ ID NO: 120 -
528 isomiR example 2 of SEQ ID NO: 120 -
529 isomiR example 1 of SEQ ID NO: 121 -
530 isomiR example 2 of SEQ ID NO: 121 -
531 isomiR example 1 of SEQ ID NO: 122 -
532 isomiR example 2 of SEQ ID NO: 122 -
533 isomiR example 1 of SEQ ID NO: 123 -
534 isomiR example 2 of SEQ ID NO: 123 -
535 isomiR example 1 of SEQ ID NO: 125 -
536 isomiR example 2 of SEQ ID NO: 125 -
537 isomiR example 1 of SEQ ID NO: 128 -
538 isomiR example 2 of SEQ ID NO: 128 -
539 isomiR example 1 of SEQ ID NO: 129 -
540 isomiR example 2 of SEQ ID NO: 129 -
541 isomiR example 1 of SEQ ID NO: 130 -
542 isomiR example 2 of SEQ ID NO: 130 -
543 isomiR example 1 of SEQ ID NO: 131 -
544 isomiR example 2 of SEQ ID NO: 131 -
545 isomiR example 1 of SEQ ID NO: 137 -
546 isomiR example 2 of SEQ ID NO: 137 -
547 isomiR example 1 of SEQ ID NO: 140 -
548 isomiR example 2 of SEQ ID NO: 140 -
549 isomiR example 1 of SEQ ID NO: 141 -
550 isomiR example 2 of SEQ ID NO: 141 -
551 isomiR example 1 of SEQ ID NO: 143 -
552 isomiR example 2 of SEQ ID NO: 143 -
553 isomiR example 1 of SEQ ID NO: 144 -
554 isomiR example 2 of SEQ ID NO: 144 -
555 isomiR example 1 of SEQ ID NO: 145 -
556 isomiR example 2 of SEQ ID NO: 145 -
557 isomiR example 1 of SEQ ID NO: 146 -
558 isomiR example 2 of SEQ ID NO: 146 -
559 isomiR example 1 of SEQ ID NO: 147 -
560 isomiR example 2 of SEQ ID NO: 147 -
561 isomiR example 1 of SEQ ID NO: 150 -
562 isomiR example 2 of SEQ ID NO: 150 -
563 isomiR example 1 of SEQ ID NO: 152 -
564 isomiR example 2 of SEQ ID NO: 152 -
565 isomiR example 1 of SEQ ID NO: 153 -
566 isomiR example 2 of SEQ ID NO: 153 -
567 isomiR example 1 of SEQ ID NO: 156 -
568 isomiR example 2 of SEQ ID NO: 156 -
569 isomiR example 1 of SEQ ID NO: 159 -
570 isomiR example 2 of SEQ ID NO: 159 -
571 isomiR example 1 of SEQ ID NO: 160 -
572 isomiR example 2 of SEQ ID NO: 160 -
573 isomiR example 1 of SEQ ID NO: 161 -
574 isomiR example 2 of SEQ ID NO: 161 -
575 isomiR example 1 of SEQ ID NO: 162 -
576 isomiR example 2 of SEQ ID NO: 162 -
577 isomiR example 1 of SEQ ID NO: 163 -
578 isomiR example 2 of SEQ ID NO: 163 -
579 isomiR example 1 of SEQ ID NO: 166 -
580 isomiR example 2 of SEQ ID NO: 166 -
581 isomiR example 1 of SEQ ID NO: 167 -
582 isomiR example 2 of SEQ ID NO: 167 -
583 isomiR example 1 of SEQ ID NO: 168 -
584 isomiR example 2 of SEQ ID NO: 168 -
585 isomiR example 1 of SEQ ID NO: 169 -
586 isomiR example 2 of SEQ ID NO: 169 -
587 isomiR example 1 of SEQ ID NO: 170 -
588 isomiR example 2 of SEQ ID NO: 170 -
589 isomiR example 1 of SEQ ID NO: 171 -
590 isomiR example 2 of SEQ ID NO: 171 -
591 isomiR example 1 of SEQ ID NO: 172 -
592 isomiR example 2 of SEQ ID NO: 172 -
593 isomiR example 1 of SEQ ID NO: 174 -
594 isomiR example 2 of SEQ ID NO: 174 -
595 isomiR example 1 of SEQ ID NO: 175 -
596 isomiR example 2 of SEQ ID NO: 175 -
597 isomiR example 1 of SEQ ID NO: 176 -
598 isomiR example 2 of SEQ ID NO: 176 -
599 isomiR example 1 of SEQ ID NO: 177 -
600 isomiR example 2 of SEQ ID NO: 177 -
601 isomiR example 1 of SEQ ID NO: 179 -
602 isomiR example 2 of SEQ ID NO: 179 -
603 isomiR example 1 of SEQ ID NO: 180 -
604 isomiR example 2 of SEQ ID NO: 180 -
605 isomiR example 1 of SEQ ID NO: 181 -
606 isomiR example 2 of SEQ ID NO: 181 -
607 isomiR example 1 of SEQ ID NO: 182 -
608 isomiR example 2 of SEQ ID NO: 182 -
609 isomiR example 1 of SEQ ID NO: 183 -
610 isomiR example 2 of SEQ ID NO: 183 -
611 isomiR example 1 of SEQ ID NO: 184 -
612 isomiR example 2 of SEQ ID NO: 184 -
613 isomiR example 1 of SEQ ID NO: 185 -
614 isomiR example 2 of SEQ ID NO: 185 -
615 isomiR example 1 of SEQ ID NO: 187 -
616 isomiR example 2 of SEQ ID NO: 187 -
617 isomiR example 1 of SEQ ID NO: 188 -
618 isomiR example 2 of SEQ ID NO: 188 -
619 isomiR example 1 of SEQ ID NO: 189 -
620 isomiR example 2 of SEQ ID NO: 189 -
621 isomiR example 1 of SEQ ID NO: 190 -
622 isomiR example 2 of SEQ ID NO: 190 -
623 isomiR example 1 of SEQ ID NO: 191 -
624 isomiR example 2 of SEQ ID NO: 191 -
625 isomiR example 1 of SEQ ID NO: 193 -
626 isomiR example 2 of SEQ ID NO: 193 -
627 isomiR example 1 of SEQ ID NO: 194 -
628 isomiR example 2 of SEQ ID NO: 194 -
629 isomiR example 1 of SEQ ID NO: 196 -
630 isomiR example 2 of SEQ ID NO: 196 -
631 isomiR example 1 of SEQ ID NO: 197 -
632 isomiR example 2 of SEQ ID NO: 197 -
633 isomiR example 1 of SEQ ID NO: 198 -
634 isomiR example 2 of SEQ ID NO: 198 -
635 hsa-miR-6794-5p MIMAT0027488
636 hsa-miR-6774-5p MIMAT0027448
637 hsa-miR-4707-3p MIMAT0019808
638 hsa-miR-4534 MIMAT0019073
639 hsa-miR-4294 MIMAT0016849
640 hsa-miR-6850-5p MIMAT0027600
641 hsa-miR-6089 MIMAT0023714
642 hsa-miR-671-5p MIMAT0003880
643 hsa-mir-6794 MI0022639
644 hsa-mir-6774 MI0022619
645 hsa-mir-4707 MI0017340
646 hsa-mir-4534 MI0016901
647 hsa-mir-4294 MI0015827
648 hsa-mir-6850 MI0022696
649 hsa-mir-6089-1 MI0020366
650 hsa-mir-6089-2 MI0023563
651 hsa-mir-671 MI0003760
652 isomiR example 1 of SEQ ID NO: 637 -
653 isomiR example 2 of SEQ ID NO: 637 -
654 isomiR example 1 of SEQ ID NO: 641 -
655 isomiR example 2 of SEQ ID NO: 641 -
656 isomiR example 1 of SEQ ID NO: 642 -
657 isomiR example 2 of SEQ ID NO: 642 -


[0260] The present specification encompasses the contents described in the specifications and/or drawings of Japanese Patent Application Nos. 2014-123224 and 2015-071485 from which the present application claims priority.

Advantageous Effects of Invention



[0261]  According to the present invention, stomach cancer can be detected easily and in high accuracy.

[0262] For example, the presence or absence of stomach cancer in a patient(s) can be easily detected by using, as an indicator(s), the measurement values of several miRNAs in blood, serum, and/or plasma of the patient(s), which can be collected with limited invasiveness.

Brief Description of Drawings



[0263] 

[Figure 1] This figure shows the relationship between the nucleotide sequences of hsa-miR-1225-3p represented by SEQ ID NO: 7 and hsa-miR-1225-5p represented by SEQ ID NO: 52, which are produced from a precursor hsa-mir-1225 represented by SEQ ID NO: 206.

[Figure 2] Left diagram: the measurement values of hsa-miR-4257 (SEQ ID NO: 1) in healthy subjects (100 persons) and stomach cancer patients (34 persons) selected as a training cohort were each plotted on the ordinate. The horizontal line in the diagram depicts a threshold (6.29) that was optimized by Fisher's discriminant analysis and discriminated between the two groups. Right diagram: the measurement values of hsa-miR-4257 (SEQ ID NO: 1) in healthy subjects (50 persons) and stomach cancer patients (16 persons) selected as a validation cohort were each plotted on the ordinate. The horizontal line in the diagram depicts the threshold (6.29) that was set in the training cohort and discriminated between the two groups.

[Figure 3] Left diagram: the measurement values of hsa-miR-4257 (SEQ ID NO: 1) in healthy subjects (100 persons, circles) and stomach cancer patients (34 persons, triangles) selected as a training cohort were each plotted on the abscissa against their measurement values of hsa-miR-6726-5p (SEQ ID NO: 2) on the ordinate. The line in the diagram depicts a discriminant function (0 = 0.83x + y - 14.78) that was optimized by Fisher's discriminant analysis and discriminated between the two groups. Right diagram: the measurement values of hsa-miR-4257 (SEQ ID NO: 1) in healthy subjects (50 persons, circles) and stomach cancer patients (16 persons, triangles) selected as a validation cohort were each plotted on the abscissa against their measurement values of hsa-miR-6726-5p (SEQ ID NO: 2) on the ordinate. The line in the diagram depicts the threshold (0 = 0.83x + y - 14.78) that was set for the training cohort and discriminated between the two groups.

[Figure 4] Upper diagram: a discriminant (2.51 × hsa-miR-6781-5p - 0.63 × hsa-miR-4419b + 0.98 × hsa-miR-940 + 0.63 × hsa-miR-4294 - 0.70 × hsa-miR-6769b-5p + 0.85 × hsa-miR-1914-3p - 37.81) was prepared by use of Fisher's discriminant analysis from the measurement values of hsa-miR-6781-5p (SEQ ID NO: 9), hsa-miR-204-3p (SEQ ID NO: 13), hsa-miR-3195 (SEQ ID NO: 143), hsa-miR-6769b-5p (SEQ ID NO: 155), hsa-miR-4665-5p (SEQ ID NO: 194), and hsa-miR-4294 (SEQ ID NO: 639) in 34 stomach cancer patients, 102 healthy subjects, 63 pancreatic cancer patients, 65 bile duct cancer patients, 35 colorectal cancer patients, 32 liver cancer patients, and 17 benign pancreaticobiliary disease patients selected as a training cohort, and discriminant scores obtained from the discriminant were plotted on the ordinate against the sample groups on the abscissa. The dotted line in the diagram depicts a discriminant boundary that offered a discriminant score of 0 and discriminated between the groups. Lower diagram: discriminant scores obtained from the discriminant prepared from the training cohort as to the measurement values of hsa-miR-6781-5p (SEQ ID NO: 9), hsa-miR-204-3p (SEQ ID NO: 13), hsa-miR-3195 (SEQ ID NO: 143), hsa-miR-6769b-5p (SEQ ID NO: 155), hsa-miR-4665-5p (SEQ ID NO: 194), and hsa-miR-4294 (SEQ ID NO: 639) in 16 stomach cancer patients, 48 healthy subjects, 37 pancreatic cancer patients, 33 bile duct cancer patients, 15 colorectal cancer patients, 20 liver cancer patients, and 4 benign pancreaticobiliary disease patients selected as a validation cohort were plotted on the ordinate against the sample groups on the abscissa. The dotted line in the diagram depicts the discriminant boundary that offered a discriminant score of 0 and discriminated between both of the groups.


Description of Embodiments



[0264] Hereinafter, the present invention will be further described in detail.

1. Target nucleic acid for stomach cancer



[0265] Primary target nucleic acids as a stomach cancer marker(s) for detecting the presence and/or absence of stomach cancer or stomach cancer cells using the nucleic acid probe(s) or the primer(s) for the detection of stomach cancer defined above according to the present invention comprises at least hsa-miR-4257, and may also comprise one or more miRNAs selected from the group consisting of hsa-miR-6726-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-6787-5p, hsa-miR-6875-5p, hsa-miR-1225-3p, hsa-miR-8063, hsa-miR-6781-5p, hsa-miR-4746-3p, hsa-miR-1908-5p, hsa-miR-6756-5p, hsa-miR-204-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-6825-5p, hsa-miR-7108-5p, hsa-miR-4792, hsa-miR-7641, hsa-miR-3188, hsa-miR-3131, hsa-miR-6780b-5p, hsa-miR-8069, hsa-miR-6840-3p, hsa-miR-8072, hsa-miR-1233-5p, hsa-miR-6887-5p, hsa-miR-1231, hsa-miR-5572, hsa-miR-6738-5p, hsa-miR-6784-5p, hsa-miR-6791-5p, hsa-miR-6749-5p, hsa-miR-6741-5p, hsa-miR-128-1-5p, hsa-miR-4419b, hsa-miR-6746-5p, hsa-miR-3184-5p, hsa-miR-3679-5p, hsa-miR-7110-5p, hsa-miR-4516, hsa-miR-6717-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-3679-3p, hsa-miR-3135b, hsa-miR-3622a-5p, hsa-miR-711, hsa-miR-4467, hsa-miR-6857-5p, hsa-miR-6515-3p, hsa-miR-1225-5p, hsa-miR-187-5p, hsa-miR-3185, hsa-miR-642b-3p, hsa-miR-1249, hsa-miR-744-5p, hsa-miR-4442, hsa-miR-1228-3p, hsa-miR-939-5p, hsa-miR-6845-5p, hsa-miR-887-3p, hsa-miR-7845-5p, hsa-miR-6729-5p, hsa-miR-4632-5p, hsa-miR-615-5p, hsa-miR-6724-5p, hsa-miR-4728-5p, hsa-miR-6732-5p, hsa-miR-6816-5p, hsa-miR-4695-5p, hsa-miR-6088, hsa-miR-7975, hsa-miR-3197, hsa-miR-6125, hsa-miR-4433-3p, hsa-miR-6727-5p, hsa-miR-4706, hsa-miR-7847-3p, hsa-miR-6805-3p, hsa-miR-6766-3p, hsa-miR-1913, hsa-miR-4649-5p, hsa-miR-602, hsa-miR-3663-3p, hsa-miR-6893-5p, hsa-miR-6861-5p, hsa-miR-4449, hsa-miR-6842-5p, hsa-miR-4454, hsa-miR-5195-3p, hsa-miR-663b, hsa-miR-6765-5p, hsa-miR-4513, hsa-miR-614, hsa-miR-6785-5p, hsa-miR-6777-5p, hsa-miR-940, hsa-miR-4741, hsa-miR-6870-5p, hsa-miR-6131, hsa-miR-150-3p, hsa-miR-4707-5p, hsa-miR-1915-3p, hsa-miR-3937, hsa-miR-937-5p, hsa-miR-4443, hsa-miR-1914-3p, hsa-miR-3620-5p, hsa-miR-1268b, hsa-miR-1227-5p, hsa-miR-6880-5p, hsa-miR-4417, hsa-miR-6802-5p, hsa-miR-6769a-5p, hsa-miR-663a, hsa-miR-6721-5p, hsa-miR-4532, hsa-miR-7977, hsa-miR-92b-5p, hsa-miR-371a-5p, hsa-miR-6126, hsa-miR-4734, hsa-miR-4665-3p, hsa-miR-423-5p, hsa-miR-1469, hsa-miR-4675, hsa-miR-1915-5p, hsa-miR-6716-5p, hsa-miR-718, hsa-miR-4281, hsa-miR-6820-5p, hsa-miR-6795-5p, hsa-miR-6779-5p, hsa-miR-7109-5p, hsa-miR-6798-5p, hsa-miR-4648, hsa-miR-8059, hsa-miR-6765-3p, hsa-miR-6132, hsa-miR-4492, hsa-miR-7107-5p, hsa-miR-3195, hsa-miR-3180, hsa-miR-296-3p, hsa-miR-564, hsa-miR-1268a, hsa-miR-6848-5p, hsa-miR-762, hsa-miR-2861, hsa-miR-1203, hsa-miR-1260b, hsa-miR-4476, hsa-miR-6885-5p, hsa-miR-6769b-5p, hsa-miR-23b-3p, hsa-miR-1343-5p, hsa-miR-3621, hsa-miR-4688, hsa-miR-4286, hsa-miR-4640-5p, hsa-miR-4739, hsa-miR-1260a, hsa-miR-4276, hsa-miR-7106, hsa-miR-6794-5p, hsa-miR-6774-5p, hsa-miR-4707-3p, hsa-miR-4534, hsa-miR-4294, hsa-miR-6850-5p, hsa-miR-6089 and hsa-miR-671-5p. Furthermore, at least one or more miRNAs selected from the group consisting of other stomach cancer markers that can be combined with these miRNAs, i.e., hsa-miR-128-2-5p, hsa-miR-125a-3p, hsa-miR-92a-2-5p, and hsa-miR-486-3p can also be preferably used as a target nucleic acid. Moreover, at least one or more miRNAs selected from the group consisting of other stomach cancer markers that can be combined with these miRNAs, i.e., hsa-miR-3196, hsa-miR-211-3p, hsa-miR-4271, hsa-miR-6851-5p, hsa-miR-149-3p, hsa-miR-4667-5p, hsa-miR-135a-3p, hsa-miR-4486, hsa-miR-4697-5p, hsa-miR-4725-3p, hsa-miR-6510-5p, hsa-miR-5001-5p, hsa-miR-4673, hsa-miR-4466, hsa-miR-23a-3p, hsa-miR-3656, hsa-miR-6782-5p, hsa-miR-4689, hsa-miR-451a, hsa-miR-4446-3p, hsa-miR-3180-3p, hsa-miR-642a-3p, hsa-miR-6889-5p, hsa-miR-3178, hsa-miR-4665-5p, hsa-miR-6722-3p, hsa-miR-30c-1-3p, hsa-miR-4507, hsa-miR-3141 and hsa-miR-1199-5p can also be preferably used as a target nucleic acid(s).

[0266] These miRNAs include, for example, a human gene comprising a nucleotide sequence represented by any of SEQ ID NOs: 1 to 199 and 635 to 642 (i.e., hsa-miR-4257, hsa-miR-6726-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-6787-5p, hsa-miR-6875-5p, hsa-miR-1225-3p, hsa-miR-8063, hsa-miR-6781-5p, hsa-miR-4746-3p, hsa-miR-1908-5p, hsa-miR-6756-5p, hsa-miR-204-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-6825-5p, hsa-miR-7108-5p, hsa-miR-4792, hsa-miR-7641, hsa-miR-3188, hsa-miR-3131, hsa-miR-6780b-5p, hsa-miR-8069, hsa-miR-6840-3p, hsa-miR-8072, hsa-miR-1233-5p, hsa-miR-6887-5p, hsa-miR-1231, hsa-miR-5572, hsa-miR-6738-5p, hsa-miR-6784-5p, hsa-miR-6791-5p, hsa-miR-6749-5p, hsa-miR-6741-5p, hsa-miR-128-1-5p, hsa-miR-4419b, hsa-miR-6746-5p, hsa-miR-3184-5p, hsa-miR-3679-5p, hsa-miR-7110-5p, hsa-miR-4516, hsa-miR-6717-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-3679-3p, hsa-miR-3135b, hsa-miR-3622a-5p, hsa-miR-711, hsa-miR-4467, hsa-miR-6857-5p, hsa-miR-6515-3p, hsa-miR-1225-5p, hsa-miR-187-5p, hsa-miR-3185, hsa-miR-642b-3p, hsa-miR-1249, hsa-miR-744-5p, hsa-miR-4442, hsa-miR-1228-3p, hsa-miR-939-5p, hsa-miR-6845-5p, hsa-miR-887-3p, hsa-miR-7845-5p, hsa-miR-6729-5p, hsa-miR-4632-5p, hsa-miR-615-5p, hsa-miR-6724-5p, hsa-miR-4728-5p, hsa-miR-6732-5p, hsa-miR-6816-5p, hsa-miR-4695-5p, hsa-miR-6088, hsa-miR-7975, hsa-miR-3197, hsa-miR-6125, hsa-miR-4433-3p, hsa-miR-6727-5p, hsa-miR-4706, hsa-miR-7847-3p, hsa-miR-6805-3p, hsa-miR-6766-3p, hsa-miR-1913, hsa-miR-4649-5p, hsa-miR-602, hsa-miR-3663-3p, hsa-miR-6893-5p, hsa-miR-6861-5p, hsa-miR-4449, hsa-miR-6842-5p, hsa-miR-4454, hsa-miR-5195-3p, hsa-miR-663b, hsa-miR-6765-5p, hsa-miR-4513, hsa-miR-614, hsa-miR-6785-5p, hsa-miR-6777-5p, hsa-miR-940, hsa-miR-4741, hsa-miR-6870-5p, hsa-miR-6131, hsa-miR-150-3p, hsa-miR-4707-5p, hsa-miR-1915-3p, hsa-miR-3937, hsa-miR-937-5p, hsa-miR-4443, hsa-miR-1914-3p, hsa-miR-3620-5p, hsa-miR-1268b, hsa-miR-1227-5p, hsa-miR-6880-5p, hsa-miR-4417, hsa-miR-6802-5p, hsa-miR-6769a-5p, hsa-miR-663a, hsa-miR-6721-5p, hsa-miR-4532, hsa-miR-7977, hsa-miR-92b-5p, hsa-miR-371a-5p, hsa-miR-6126, hsa-miR-4734, hsa-miR-4665-3p, hsa-miR-423-5p, hsa-miR-1469, hsa-miR-4675, hsa-miR-1915-5p, hsa-miR-6716-5p, hsa-miR-718, hsa-miR-4281, hsa-miR-6820-5p, hsa-miR-6795-5p, hsa-miR-6779-5p, hsa-miR-7109-5p, hsa-miR-6798-5p, hsa-miR-4648, hsa-miR-8059, hsa-miR-6765-3p, hsa-miR-6132, hsa-miR-4492, hsa-miR-7107-5p, hsa-miR-3195, hsa-miR-3180, hsa-miR-296-3p, hsa-miR-564, hsa-miR-1268a, hsa-miR-6848-5p, hsa-miR-762, hsa-miR-2861, hsa-miR-1203, hsa-miR-1260b, hsa-miR-4476, hsa-miR-6885-5p, hsa-miR-6769b-5p, hsa-miR-23b-3p, hsa-miR-1343-5p, hsa-miR-3621, hsa-miR-4688, hsa-miR-4286, hsa-miR-4640-5p, hsa-miR-4739, hsa-miR-1260a, hsa-miR-4276, hsa-miR-7106, hsa-miR-6794-5p, hsa-miR-6774-5p, hsa-miR-4707-3p, hsa-miR-4534, hsa-miR-4294, hsa-miR-6850-5p, hsa-miR-6089, hsa-miR-671-5p, hsa-miR-128-2-5p, hsa-miR-125a-3p, hsa-miR-92a-2-5p, hsa-miR-486-3p, hsa-miR-3196, hsa-miR-211-3p, hsa-miR-4271, hsa-miR-6851-5p, hsa-miR-149-3p, hsa-miR-4667-5p, hsa-miR-135a-3p, hsa-miR-4486, hsa-miR-4697-5p, hsa-miR-4725-3p, hsa-miR-6510-5p, hsa-miR-5001-5p, hsa-miR-4673, hsa-miR-4466, hsa-miR-23a-3p, hsa-miR-3656, hsa-miR-6782-5p, hsa-miR-4689, hsa-miR-451a, hsa-miR-4446-3p, hsa-miR-3180-3p, hsa-miR-642a-3p, hsa-miR-6889-5p, hsa-miR-3178, hsa-miR-4665-5p, hsa-miR-6722-3p, hsa-miR-30c-1-3p, hsa-miR-4507, hsa-miR-3141 and hsa-miR-1199-5p, respectively), a congener thereof, a transcript thereof, and a variant or a derivative thereof. In this context, the gene, the congener, the transcript, the variant, and the derivative are as defined above.

[0267] The target nucleic acid is a human gene comprising a nucleotide sequence represented by SEQ ID NO: 1, optionally together with any of SEQ ID NOs: 2 to 657, or a transcript thereof, more preferably the transcript, i.e., a miRNA or its precursor RNA (pri-miRNA or pre-miRNA).

[0268] The first target gene is the hsa-miR-4257 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0269]  The second target gene is the hsa-miR-6726-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0270] The third target gene is the hsa-miR-1343-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0271] The fourth target gene is the hsa-miR-1247-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0272] The fifth target gene is the hsa-miR-6787-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0273] The sixth target gene is the hsa-miR-6875-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0274] The seventh target gene is the hsa-miR-1225-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0275] The eighth target gene is the hsa-miR-8063 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0276]  The ninth target gene is the hsa-miR-6781-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0277] The 10th target gene is the hsa-miR-4746-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0278] The 11th target gene is the hsa-miR-1908-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0279] The 12th target gene is the hsa-miR-6756-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0280] The 13th target gene is the hsa-miR-204-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0281] The 14th target gene is the hsa-miR-4651 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0282] The 15th target gene is the hsa-miR-6757-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0283] The 16th target gene is the hsa-miR-6825-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0284] The 17th target gene is the hsa-miR-7108-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0285] The 18th target gene is the hsa-miR-4792 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0286] The 19th target gene is the hsa-miR-7641 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0287] The 20th target gene is the hsa-miR-3188 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0288] The 21st target gene is the hsa-miR-3131 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0289] The 22nd target gene is the hsa-miR-6780b-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0290] The 23rd target gene is the hsa-miR-8069 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0291]  The 24th target gene is the hsa-miR-6840-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0292] The 25th target gene is the hsa-miR-8072 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0293] The 26th target gene is the hsa-miR-1233-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0294] The 27th target gene is the hsa-miR-6887-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0295] The 28th target gene is the hsa-miR-1231 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0296] The 29th target gene is the hsa-miR-5572 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0297] The 30th target gene is the hsa-miR-6738-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0298] The 31st target gene is the hsa-miR-6784-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0299] The 32nd target gene is the hsa-miR-6791-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0300] The 33rd target gene is the hsa-miR-6749-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0301] The 34th target gene is the hsa-miR-6741-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0302] The 35th target gene is the hsa-miR-128-1-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0303] The 36th target gene is the hsa-miR-4419b gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0304] The 37th target gene is the hsa-miR-6746-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0305] The 38th target gene is the hsa-miR-3184-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0306]  The 39th target gene is the hsa-miR-3679-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0307] The 40th target gene is the hsa-miR-7110-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0308] The 41st target gene is the hsa-miR-4516 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0309] The 42nd target gene is the hsa-miR-6717-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0310] The 43rd target gene is the hsa-miR-6826-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0311] The 44th target gene is the hsa-miR-4433b-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0312] The 45th target gene is the hsa-miR-3679-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0313] The 46th target gene is the hsa-miR-3135b gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0314] The 47th target gene is the hsa-miR-3622a-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0315] The 48th target gene is the hsa-miR-711 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0316] The 49th target gene is the hsa-miR-4467 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0317] The 50th target gene is the hsa-miR-6857-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0318] The 51st target gene is the hsa-miR-6515-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0319] The 52nd target gene is the hsa-miR-1225-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0320] The 53rd target gene is the hsa-miR-187-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0321]  The 54th target gene is the hsa-miR-3185 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0322] The 55th target gene is the hsa-miR-642b-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0323] The 56th target gene is the hsa-miR-1249 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0324] The 57th target gene is the hsa-miR-744-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0325] The 58th target gene is the hsa-miR-4442 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0326] The 59th target gene is the hsa-miR-1228-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0327] The 60th target gene is the hsa-miR-939-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0328] The 61st target gene is the hsa-miR-6845-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0329] The 62nd target gene is the hsa-miR-887-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0330] The 63rd target gene is the hsa-miR-7845-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0331] The 64th target gene is the hsa-miR-6729-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0332] The 65th target gene is the hsa-miR-4632-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0333] The 66th target gene is the hsa-miR-615-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0334] The 67th target gene is the hsa-miR-6724-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0335] The 68th target gene is the hsa-miR-4728-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0336]  The 69th target gene is the hsa-miR-6732-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0337] The 70th target gene is the hsa-miR-6816-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0338] The 71st target gene is the hsa-miR-4695-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0339] The 72nd target gene is the hsa-miR-6088 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0340] The 73rd target gene is the hsa-miR-7975 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0341] The 74th target gene is the hsa-miR-3197 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0342] The 75th target gene is the hsa-miR-6125 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0343] The 76th target gene is the hsa-miR-4433-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0344] The 77th target gene is the hsa-miR-6727-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0345] The 78th target gene is the hsa-miR-4706 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0346] The 79th target gene is the hsa-miR-7847-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0347] The 80th target gene is the hsa-miR-6805-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0348] The 81st target gene is the hsa-miR-6766-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0349] The 82nd target gene is the hsa-miR-1913 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0350] The 83rd target gene is the hsa-miR-4649-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0351]  The 84th target gene is the hsa-miR-602 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0352] The 85th target gene is the hsa-miR-3663-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0353] The 86th target gene is the hsa-miR-6893-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0354] The 87th target gene is the hsa-miR-6861-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0355] The 88th target gene is the hsa-miR-4449 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0356] The 89th target gene is the hsa-miR-6842-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0357] The 90th target gene is the hsa-miR-4454 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0358] The 91st target gene is the hsa-miR-5195-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0359] The 92nd target gene is the hsa-miR-663b gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0360] The 93rd target gene is the hsa-miR-6765-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0361] The 94th target gene is the hsa-miR-4513 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0362] The 95th target gene is the hsa-miR-614 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0363] The 96th target gene is the hsa-miR-6785-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0364] The 97th target gene is the hsa-miR-6777-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0365] The 98th target gene is the hsa-miR-940 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0366]  The 99th target gene is the hsa-miR-4741 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0367] The 100th target gene is the hsa-miR-6870-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0368] The 101st target gene is the hsa-miR-6131 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0369] The 102nd target gene is the hsa-miR-150-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0370] The 103rd target gene is the hsa-miR-4707-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0371] The 104th target gene is the hsa-miR-1915-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0372] The 105th target gene is the hsa-miR-3937 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0373] The 106th target gene is the hsa-miR-937-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0374] The 107th target gene is the hsa-miR-4443 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0375] The 108th target gene is the hsa-miR-1914-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0376] The 109th target gene is the hsa-miR-3620-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0377] The 110th target gene is the hsa-miR-1268b gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0378] The 111th target gene is the hsa-miR-1227-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0379] The 112th target gene is the hsa-miR-6880-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0380] The 113th target gene is the hsa-miR-4417 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0381]  The 114th target gene is the hsa-miR-6802-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0382] The 115th target gene is the hsa-miR-6769a-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0383] The 116th target gene is the hsa-miR-663a gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0384] The 117th target gene is the hsa-miR-6721-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0385] The 118th target gene is the hsa-miR-4532 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0386] The 119th target gene is the hsa-miR-7977 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0387] The 120th target gene is the hsa-miR-92b-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0388] The 121st target gene is the hsa-miR-371a-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0389] The 122nd target gene is the hsa-miR-6126 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0390] The 123rd target gene is the hsa-miR-4734 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0391] The 124th target gene is the hsa-miR-4665-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0392] The 125th target gene is the hsa-miR-423-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0393] The 126th target gene is the hsa-miR-1469 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0394] The 127th target gene is the hsa-miR-4675 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0395] The 128th target gene is the hsa-miR-1915-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0396]  The 129th target gene is the hsa-miR-6716-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0397] The 130th target gene is the hsa-miR-718 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0398] The 131st target gene is the hsa-miR-4281 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0399] The 132nd target gene is the hsa-miR-6820-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0400] The 133rd target gene is the hsa-miR-6795-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0401] The 134th target gene is the hsa-miR-6779-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0402] The 135th target gene is the hsa-miR-7109-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0403] The 136th target gene is the hsa-miR-6798-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0404] The 137th target gene is the hsa-miR-4648 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0405] The 138th target gene is the hsa-miR-8059 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0406] The 139th target gene is the hsa-miR-6765-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0407] The 140th target gene is the hsa-miR-6132 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0408] The 141st target gene is the hsa-miR-4492 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0409] The 142nd target gene is the hsa-miR-7107-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0410] The 143rd target gene is the hsa-miR-3195 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0411]  The 144th target gene is the hsa-miR-3180 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0412] The 145th target gene is the hsa-miR-296-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0413] The 146th target gene is the hsa-miR-564 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0414] The 147th target gene is the hsa-miR-1268a gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0415] The 148th target gene is the hsa-miR-6848-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0416] The 149th target gene is the hsa-miR-762 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0417] The 150th target gene is the hsa-miR-2861 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0418] The 151st target gene is the hsa-miR-1203 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0419] The 152nd target gene is the hsa-miR-1260b gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0420] The 153rd target gene is the hsa-miR-4476 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0421] The 154th target gene is the hsa-miR-6885-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0422] The 155th target gene is the hsa-miR-6769b-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0423] The 156th target gene is the hsa-miR-23b-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0424] The 157th target gene is the hsa-miR-1343-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0425] The 158th target gene is the hsa-miR-3621 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0426]  The 159th target gene is the hsa-miR-4688 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0427] The 160th target gene is the hsa-miR-4286 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0428] The 161st target gene is the hsa-miR-4640-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0429] The 162nd target gene is the hsa-miR-4739 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0430] The 163rd target gene is the hsa-miR-1260a gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0431] The 164th target gene is the hsa-miR-4276 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0432] The 165th target gene is the hsa-miR-7106-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0433] The 166th target gene is the hsa-miR-128-2-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the hsa-miR-128b (hsa-miR-128-2-3p) gene, which is derived from the same precursor, or the transcript thereof can serve as a marker for stomach cancer (Patent Literature 2).

[0434] The 167th target gene is the hsa-miR-125a-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer (Patent Literature 1).

[0435] The 168th target gene is the hsa-miR-92a-2-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the hsa-miR-92-2 (hsa-miR-92a-2-3p) gene, which is derived from the same precursor, or the transcript thereof can serve as a marker for stomach cancer (Patent Literature 2).

[0436] The 169th target gene is the hsa-miR-486-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the hsa-miR-486-5p gene, which is derived from the same precursor, or the transcript thereof can serve as a marker for stomach cancer (Patent Literature 3).

[0437] The 170th target gene is the hsa-miR-3196 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0438] The 171st target gene is the hsa-miR-211-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the hsa-miR-211 (hsa-miR-211-5p) gene, which is derived from the same precursor, or the transcript thereof can serve as a marker for stomach cancer (Patent Literature 2).

[0439] The 172nd target gene is the hsa-miR-4271 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0440]  The 173rd target gene is the hsa-miR-6851-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0441] The 174th target gene is the hsa-miR-149-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0442] The 175th target gene is the hsa-miR-4667-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0443] The 176th target gene is the hsa-miR-135a-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0444] The 177th target gene is the hsa-miR-4486 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0445] The 178th target gene is the hsa-miR-4697-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0446] The 179th target gene is the hsa-miR-4725-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0447] The 180th target gene is the hsa-miR-6510-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0448] The 181st target gene is the hsa-miR-5001-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0449] The 182nd target gene is the hsa-miR-4673 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0450] The 183rd target gene is the hsa-miR-4466 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0451] The 184th target gene is the hsa-miR-23a-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer (Patent Literature 2).

[0452] The 185th target gene is the hsa-miR-3656 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0453] The 186th target gene is the hsa-miR-6782-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0454] The 187th target gene is the hsa-miR-4689 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0455]  The 188th target gene is the hsa-miR-451a gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer (Patent Literature 3).

[0456] The 189th target gene is the hsa-miR-4446-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0457] The 190th target gene is the hsa-miR-3180-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0458] The 191st target gene is the hsa-miR-642a-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0459] The 192nd target gene is the hsa-miR-6889-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0460] The 193rd target gene is the hsa-miR-3178 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0461] The 194th target gene is the hsa-miR-4665-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0462] The 195th target gene is the hsa-miR-6722-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0463] The 196th target gene is the hsa-miR-30c-1-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. The previously known report shows that change in the expression of the hsa-miR-30c (hsa-miR-30c-1-5p) gene, which is derived from the same precursor, or the transcript thereof can serve as a marker for stomach cancer (Patent Literature 2).

[0464] The 197th target gene is the hsa-miR-4507 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0465] The 198th target gene is the hsa-miR-3141 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0466] The 199th target gene is the hsa-miR-1199-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0467] The 200th target gene is the hsa-miR-6794-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0468] The 201st target gene is the hsa-miR-6774-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0469] The 202nd target gene is the hsa-miR-4707-3p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0470]  The 203rd target gene is the hsa-miR-4534 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0471] The 204th target gene is the hsa-miR-4294 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0472] The 205th target gene is the hsa-miR-6850-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0473] The 206th target gene is the hsa-miR-6089 gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

[0474] The 207th target gene is the hsa-miR-671-5p gene, a congener thereof, a transcript thereof, or a variant or a derivative thereof. None of the previously known reports show that change in the expression of the gene or the transcript thereof can serve as a marker for stomach cancer.

2. Nucleic acid probe or primer for detection of stomach cancer



[0475] In the present invention, a nucleic acid(s) capable of specifically binding to any of the target nucleic acid(s) as the stomach cancer marker(s) described above can be used as a nucleic acid(s), for example, a nucleic acid probe(s) or a primer(s), for the detection or diagnosis of stomach cancer.

[0476] In the present invention, the nucleic acid probe(s) or the primer(s) that can be used for detecting stomach cancer or for diagnosing stomach cancer enables qualitative and/or quantitative measurement of the presence, expression level, or abundance of any of the target nucleic acids as the stomach cancer markers described above, for example: human-derived hsa-miR-4257, optionally together with hsa-miR-6726-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-6787-5p, hsa-miR-6875-5p, hsa-miR-1225-3p, hsa-miR-8063, hsa-miR-6781-5p, hsa-miR-4746-3p, hsa-miR-1908-5p, hsa-miR-6756-5p, hsa-miR-204-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-6825-5p, hsa-miR-7108-5p, hsa-miR-4792, hsa-miR-7641, hsa-miR-3188, hsa-miR-3131, hsa-miR-6780b-5p, hsa-miR-8069, hsa-miR-6840-3p, hsa-miR-8072, hsa-miR-1233-5p, hsa-miR-6887-5p, hsa-miR-1231, hsa-miR-5572, hsa-miR-6738-5p, hsa-miR-6784-5p, hsa-miR-6791-5p, hsa-miR-6749-5p, hsa-miR-6741-5p, hsa-miR-128-1-5p, hsa-miR-4419b, hsa-miR-6746-5p, hsa-miR-3184-5p, hsa-miR-3679-5p, hsa-miR-7110-5p, hsa-miR-4516, hsa-miR-6717-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-3679-3p, hsa-miR-3135b, hsa-miR-3622a-5p, hsa-miR-711, hsa-miR-4467, hsa-miR-6857-5p, hsa-miR-6515-3p, hsa-miR-1225-5p, hsa-miR-187-5p, hsa-miR-3185, hsa-miR-642b-3p, hsa-miR-1249, hsa-miR-744-5p, hsa-miR-4442, hsa-miR-1228-3p, hsa-miR-939-5p, hsa-miR-6845-5p, hsa-miR-887-3p, hsa-miR-7845-5p, hsa-miR-6729-5p, hsa-miR-4632-5p, hsa-miR-615-5p, hsa-miR-6724-5p, hsa-miR-4728-5p, hsa-miR-6732-5p, hsa-miR-6816-5p, hsa-miR-4695-5p, hsa-miR-6088, hsa-miR-7975, hsa-miR-3197, hsa-miR-6125, hsa-miR-4433-3p, hsa-miR-6727-5p, hsa-miR-4706, hsa-miR-7847-3p, hsa-miR-6805-3p, hsa-miR-6766-3p, hsa-miR-1913, hsa-miR-4649-5p, hsa-miR-602, hsa-miR-3663-3p, hsa-miR-6893-5p, hsa-miR-6861-5p, hsa-miR-4449, hsa-miR-6842-5p, hsa-miR-4454, hsa-miR-5195-3p, hsa-miR-663b, hsa-miR-6765-5p, hsa-miR-4513, hsa-miR-614, hsa-miR-6785-5p, hsa-miR-6777-5p, hsa-miR-940, hsa-miR-4741, hsa-miR-6870-5p, hsa-miR-6131, hsa-miR-150-3p, hsa-miR-4707-5p, hsa-miR-1915-3p, hsa-miR-3937, hsa-miR-937-5p, hsa-miR-4443, hsa-miR-1914-3p, hsa-miR-3620-5p, hsa-miR-1268b, hsa-miR-1227-5p, hsa-miR-6880-5p, hsa-miR-4417, hsa-miR-6802-5p, hsa-miR-6769a-5p, hsa-miR-663a, hsa-miR-6721-5p, hsa-miR-4532, hsa-miR-7977, hsa-miR-92b-5p, hsa-miR-371a-5p, hsa-miR-6126, hsa-miR-4734, hsa-miR-4665-3p, hsa-miR-423-5p, hsa-miR-1469, hsa-miR-4675, hsa-miR-1915-5p, hsa-miR-6716-5p, hsa-miR-718, hsa-miR-4281, hsa-miR-6820-5p, hsa-miR-6795-5p, hsa-miR-6779-5p, hsa-miR-7109-5p, hsa-miR-6798-5p, hsa-miR-4648, hsa-miR-8059, hsa-miR-6765-3p, hsa-miR-6132, hsa-miR-4492, hsa-miR-7107-5p, hsa-miR-3195, hsa-miR-3180, hsa-miR-296-3p, hsa-miR-564, hsa-miR-1268a, hsa-miR-6848-5p, hsa-miR-762, hsa-miR-2861, hsa-miR-1203, hsa-miR-1260b, hsa-miR-4476, hsa-miR-6885-5p, hsa-miR-6769b-5p, hsa-miR-23b-3p, hsa-miR-1343-5p, hsa-miR-3621, hsa-miR-4688, hsa-miR-4286, hsa-miR-4640-5p, hsa-miR-4739, hsa-miR-1260a, hsa-miR-4276, hsa-miR-7106, hsa-miR-6794-5p, hsa-miR-6774-5p, hsa-miR-4707-3p, hsa-miR-4534, hsa-miR-4294, hsa-miR-6850-5p, hsa-miR-6089 and hsa-miR-671-5p or a combination thereof, congeners thereof, transcripts thereof, or variants or derivatives thereof; and, optionally combined therewith, hsa-miR-128-2-5p, hsa-miR-125a-3p, hsa-miR-92a-2-5p, and hsa-miR-486-3p or a combination thereof, congeners thereof, transcripts thereof, or variants or derivatives thereof; and, optionally combined therewith, hsa-miR-3196, hsa-miR-211-3p, hsa-miR-4271, hsa-miR-6851-5p, hsa-miR-149-3p, hsa-miR-4667-5p, hsa-miR-135a-3p, hsa-miR-4486, hsa-miR-4697-5p, hsa-miR-4725-3p, hsa-miR-6510-5p, hsa-miR-5001-5p, hsa-miR-4673, hsa-miR-4466, hsa-miR-23a-3p, hsa-miR-3656, hsa-miR-6782-5p, hsa-miR-4689, hsa-miR-451a, hsa-miR-4446-3p, hsa-miR-3180-3p, hsa-miR-642a-3p, hsa-miR-6889-5p, hsa-miR-3178, hsa-miR-4665-5p, hsa-miR-6722-3p, hsa-miR-30c-1-3p, hsa-miR-4507, hsa-miR-3141 and hsa-miR-1199-5p or a combination thereof, congeners thereof, transcripts thereof, or variants or derivatives thereof.

[0477] The expression level of each target nucleic acid described above is increased or decreased (hereinafter, referred to as "increased/decreased") depending on the type of the target nucleic acid in a subject having stomach cancer as compared with a healthy subject. Hence, the nucleic acid of the present invention can be effectively used for measuring the expression level of the target nucleic acid described above in a body fluid derived from a subject (e.g., a human) suspected of having stomach cancer and a body fluid derived from a healthy subject and thereby detecting stomach cancer by the comparison thereof.

[0478] The nucleic acid probe(s) or the primer(s) that can be used in the present invention is a nucleic acid probe(s) capable of specifically binding to at least one polynucleotide consisting of a nucleotide sequence represented SEQ ID NO: 1, optionally together with any of SEQ ID NOs :2 to 165 and 635 to 642, or a primer for amplifying at least one polynucleotide consisting of a nucleotide sequence represented SEQ ID NO: 1, optionally together with any of SEQ ID NOs :2 to 165 and 635 to 642.

[0479] The nucleic acid probe(s) or the primer(s) that can be used in the present invention may further comprise a nucleic acid probe capable of specifically binding to at least one polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169, or a primer for amplifying at least one polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169.

[0480]  The nucleic acid probe(s) or the primer(s) that can be used in the present invention may further comprise a nucleic acid probe capable of specifically binding to at least one polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199, or a primer for amplifying at least one polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199.

[0481] Specifically, these nucleic acid probes or primers comprise SEQ ID NO: 1 optionally together with a combination of one or more polynucleotides selected from a group of polynucleotides comprising nucleotide sequences represented by any of SEQ ID NOs: 2 to 657, or nucleotide sequences derived from the nucleotide sequences by the replacement of u with t, and a group of complementary polynucleotides thereof, a group of polynucleotides respectively hybridizing under stringent conditions (mentioned later) to DNAs consisting of nucleotide sequences complementary to these nucleotide sequences, and a group of complementary polynucleotides thereof, and a group of polynucleotides comprising 15 or more, preferably 17 or more consecutive nucleotides in the nucleotide sequences of these polynucleotide groups. These polynucleotides can be used as nucleic acid probes and primers for detecting the stomach cancer markers as target nucleic acids.

[0482] More specifically, examples of the nucleic acid probe(s) or the primer(s) that can be used in the present invention include one or more polynucleotides selected from the group consisting of the following polynucleotides (a) to (e):
  1. (a) a polynucleotide consisting of a nucleotide sequence represented by SEQ ID NO: 1, optionally together with any of SEQ ID NOs 2 to 165 and 635 to 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,
  2. (b) a polynucleotide comprising a nucleotide sequence represented by SEQ ID NO: 1, optionally together with any of SEQ ID NOs 2 to 165 and 635 to 642,
  3. (c) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by SEQ ID NO: 1, optionally together with any of SEQ ID NOs 2 to 165 and 635 to 642, or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,
  4. (d) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NO: 1, optionally together with any of SEQ ID NOs 2 to 165 and 635 to 642, or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, and
  5. (e) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a) to (d).


[0483] In addition to at least one or more polynucleotides selected from the group consisting of the polynucleotides (a) to (e), the nucleic acid probe(s) or the primer(s) that can be used in the present invention may further comprise polynucleotides selected from the group consisting of the following polynucleotides (f) to (j):

(f) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(g) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169,

(h) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(i) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, and

(j) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (f) to (i).



[0484] In addition to at least one or more polynucleotide(s) selected from the group consisting of the polynucleotides (a) to (j), the nucleic acid probe(s) or the primer(s) that can be used in the present invention may further comprise polynucleotides selected from the group consisting of the following polynucleotides (k) to (o):

(k) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(1) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199,

(m) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(n) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, and

(o) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (k) to (n).



[0485] For the above-mentioned polynucleotides, the "fragment thereof comprising 15 or more consecutive nucleotides" can comprise, but not limited to, the number of nucleotides in the range from, for example, 15 consecutive nucleotides to less than the total number of nucleotides of the sequence, from 17 consecutive nucleotides to less than the total number of nucleotides of the sequence, or from 19 consecutive nucleotides to less than the total number of nucleotides of the sequence, or the like, in the nucleotide sequence of each polynucleotide.

[0486] These polynucleotides or fragments thereof used in the present invention may each be DNA or may each be RNA.

[0487] The polynucleotides that can be used in the present invention can each be prepared by use of a general technique such as a DNA recombination technique, PCR, or a method using an automatic DNA/RNA synthesizer.

[0488] The DNA recombination technique and the PCR method may employ a technique described in, for example, Ausubel et al., Current Protocols in Molecular Biology, John Willey & Sons, US (1993); and Sambrook et al., Molecular Cloning - A Laboratory Manual, Cold Spring Harbor Laboratory Press, US (1989).

[0489] The human-derived hsa-miR-4257, hsa-miR-6726-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-6787-5p, hsa-miR-6875-5p, hsa-miR-1225-3p, hsa-miR-8063, hsa-miR-6781-5p, hsa-miR-4746-3p, hsa-miR-1908-5p, hsa-miR-6756-5p, hsa-miR-204-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-6825-5p, hsa-miR-7108-5p, hsa-miR-4792, hsa-miR-7641, hsa-miR-3188, hsa-miR-3131, hsa-miR-6780b-5p, hsa-miR-8069, hsa-miR-6840-3p, hsa-miR-8072, hsa-miR-1233-5p, hsa-miR-6887-5p, hsa-miR-1231, hsa-miR-5572, hsa-miR-6738-5p, hsa-miR-6784-5p, hsa-miR-6791-5p, hsa-miR-6749-5p, hsa-miR-6741-5p, hsa-miR-128-1-5p, hsa-miR-4419b, hsa-miR-6746-5p, hsa-miR-3184-5p, hsa-miR-3679-5p, hsa-miR-7110-5p, hsa-miR-4516, hsa-miR-6717-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-3679-3p, hsa-miR-3135b, hsa-miR-3622a-5p, hsa-miR-711, hsa-miR-4467, hsa-miR-6857-5p, hsa-miR-6515-3p, hsa-miR-1225-5p, hsa-miR-187-5p, hsa-miR-3185, hsa-miR-642b-3p, hsa-miR-1249, hsa-miR-744-5p, hsa-miR-4442, hsa-miR-1228-3p, hsa-miR-939-5p, hsa-miR-6845-5p, hsa-miR-887-3p, hsa-miR-7845-5p, hsa-miR-6729-5p, hsa-miR-4632-5p, hsa-miR-615-5p, hsa-miR-6724-5p, hsa-miR-4728-5p, hsa-miR-6732-5p, hsa-miR-6816-5p, hsa-miR-4695-5p, hsa-miR-6088, hsa-miR-7975, hsa-miR-3197, hsa-miR-6125, hsa-miR-4433-3p, hsa-miR-6727-5p, hsa-miR-4706, hsa-miR-7847-3p, hsa-miR-6805-3p, hsa-miR-6766-3p, hsa-miR-1913, hsa-miR-4649-5p, hsa-miR-602, hsa-miR-3663-3p, hsa-miR-6893-5p, hsa-miR-6861-5p, hsa-miR-4449, hsa-miR-6842-5p, hsa-miR-4454, hsa-miR-5195-3p, hsa-miR-663b, hsa-miR-6765-5p, hsa-miR-4513, hsa-miR-614, hsa-miR-6785-5p, hsa-miR-6777-5p, hsa-miR-940, hsa-miR-4741, hsa-miR-6870-5p, hsa-miR-6131, hsa-miR-150-3p, hsa-miR-4707-5p, hsa-miR-1915-3p, hsa-miR-3937, hsa-miR-937-5p, hsa-miR-4443, hsa-miR-1914-3p, hsa-miR-3620-5p, hsa-miR-1268b, hsa-miR-1227-5p, hsa-miR-6880-5p, hsa-miR-4417, hsa-miR-6802-5p, hsa-miR-6769a-5p, hsa-miR-663a, hsa-miR-6721-5p, hsa-miR-4532, hsa-miR-7977, hsa-miR-92b-5p, hsa-miR-371a-5p, hsa-miR-6126, hsa-miR-4734, hsa-miR-4665-3p, hsa-miR-423-5p, hsa-miR-1469, hsa-miR-4675, hsa-miR-1915-5p, hsa-miR-6716-5p, hsa-miR-718, hsa-miR-4281, hsa-miR-6820-5p, hsa-miR-6795-5p, hsa-miR-6779-5p, hsa-miR-7109-5p, hsa-miR-6798-5p, hsa-miR-4648, hsa-miR-8059, hsa-miR-6765-3p, hsa-miR-6132, hsa-miR-4492, hsa-miR-7107-5p, hsa-miR-3195, hsa-miR-3180, hsa-miR-296-3p, hsa-miR-564, hsa-miR-1268a, hsa-miR-6848-5p, hsa-miR-762, hsa-miR-2861, hsa-miR-1203, hsa-miR-1260b, hsa-miR-4476, hsa-miR-6885-5p, hsa-miR-6769b-5p, hsa-miR-23b-3p, hsa-miR-1343-5p, hsa-miR-3621, hsa-miR-4688, hsa-miR-4286, hsa-miR-4640-5p, hsa-miR-4739, hsa-miR-1260a, hsa-miR-4276, hsa-miR-7106, hsa-miR-6794-5p, hsa-miR-6774-5p, hsa-miR-4707-3p, hsa-miR-4534, hsa-miR-4294, hsa-miR-6850-5p, hsa-miR-6089 and hsa-miR-671-5p, hsa-miR-128-2-5p, hsa-miR-125a-3p, hsa-miR-92a-2-5p, hsa-miR-486-3p, hsa-miR-3196, hsa-miR-211-3p, hsa-miR-4271, hsa-miR-6851-5p, hsa-miR-149-3p, hsa-miR-4667-5p, hsa-miR-135a-3p, hsa-miR-4486, hsa-miR-4697-5p, hsa-miR-4725-3p, hsa-miR-6510-5p, hsa-miR-5001-5p, hsa-miR-4673, hsa-miR-4466, hsa-miR-23a-3p, hsa-miR-3656, hsa-miR-6782-5p, hsa-miR-4689, hsa-miR-451a, hsa-miR-4446-3p, hsa-miR-3180-3p, hsa-miR-642a-3p, hsa-miR-6889-5p, hsa-miR-3178, hsa-miR-4665-5p, hsa-miR-6722-3p, hsa-miR-30c-1-3p, hsa-miR-4507, hsa-miR-3141 and hsa-miR-1199-5p represented by SEQ ID NOs: 1 to 199 and 635 to 642 are known in the art, and their acquisition methods are also known as mentioned above. Therefore, each polynucleotide that can be used as a nucleic acid probe(s) or a primer(s) in the present invention can be prepared by cloning the gene.

[0490] Such a nucleic acid probe(s) or a primer(s) can be chemically synthesized using an automatic DNA synthesizer. In general, a phosphoramidite method is used in this synthesis, and single-stranded DNA up to approximately 100 nucleotides can be automatically synthesized by this method. The automatic DNA synthesizer is commercially available from, for example, Polygen GmbH, ABI, or Applied Biosystems, Inc.

[0491] Alternatively, the polynucleotide of the present invention can also be prepared by a cDNA cloning method. The cDNA cloning technique may employ, for example, microRNA Cloning Kit Wako.

[0492] In this context, the sequences of the nucleic acid probe(s) and the primer(s) for detecting the polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 199 and 635 to 642 do not exist as miRNAs or precursors thereof in the living body or in vivo. For example, the nucleotide sequences represented by SEQ ID NO: 7 and SEQ ID NO: 52 are produced from the precursor represented by SEQ ID NO: 206. This precursor has a hairpin-like structure as shown in Figure 1, and the nucleotide sequences represented by SEQ ID NO: 7 and SEQ ID NO: 52 have mismatch sequences with each other. As such, a nucleotide sequence completely complementary to the nucleotide sequence represented by SEQ ID NO: 7 or SEQ ID NO: 52 is not naturally produced in vivo. Therefore, the nucleic acid probe and the primer for detecting the nucleotide sequence represented by any of SEQ ID NOs: 1 to 199 and 635 to 642 each have an artificial nucleotide sequence that does not exist in the living body or in vivo.

3. Kit or device for detection of stomach cancer



[0493] The present invention also provides the use of a kit or a device for the detection of stomach cancer, comprising one or more polynucleotides (which may include a variant, a fragment, or a derivative thereof; hereinafter, also referred to as a polynucleotide for detection) that can be used as a nucleic acid probe(s) or a primer(s) in the present invention for measuring a target nucleic acid(s) as a stomach cancer marker(s).

[0494] The target nucleic acid(s) as a stomach cancer marker(s) according to the present invention comprises miR-4257 and may further include target nucleic acid(s) selected from the following group 1:
miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 and miR-671-5p.

[0495] Additional target nucleic acid(s) that may be optionally used in the measurement is preferably selected from the following group 2: miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, and miR-486-3p. Additional target nucleic acid(s) that may be optionally further used in the measurement is preferably selected from the following group 3: miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 and miR-1199-5p.

[0496] The kit or the device of the present invention comprises a nucleic acid(s) capable of specifically binding to miR-4257, optionally together with any of the target nucleic acids as the stomach cancer markers described above, preferably one or more polynucleotides selected from the nucleic acid probes or the primers described in the preceding Section 2, specifically, the polynucleotides described in the preceding Section 2 or variant(s) thereof.

[0497] Specifically, the kit or the device of the present invention comprises a nucleotide sequence represented SEQ ID NO: 1, optionally together with any of SEQ ID NOs: 2 to 165 and 635 to 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, polynucleotide(s) comprising (or consisting of) a complementary sequence thereof, polynucleotide(s) hybridizing under stringent conditions to any of these polynucleotides, or variant(s) or fragment(s) comprising 15 or more consecutive nucleotides of any of these polynucleotide sequences.

[0498] The kit or the device of the present invention can further comprise one or more polynucleotides comprising (or consisting of) a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, polynucleotide(s) comprising (or consisting of) a complementary sequence thereof, polynucleotide(s) hybridizing under stringent conditions to any of these polynucleotides, variant(s) or fragment(s) comprising 15 or more consecutive nucleotides of any of these polynucleotide sequences.

[0499] The kit or the device of the present invention can further comprise one or more polynucleotides comprising (or consisting of) a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, polynucleotide(s) comprising (or consisting of) a complementary sequence thereof, polynucleotide(s) hybridizing under stringent conditions to any of these polynucleotides, variant(s) or fragment(s) comprising 15 or more consecutive nucleotides of any of these polynucleotide sequences.

[0500] The fragment(s) that can be contained in the kit or the device of the present invention is, for example, one or more, preferably two or more polynucleotides selected from the group consisting of the following polynucleotides (1) to (3):
  1. (1) a polynucleotide comprising 15 or more consecutive nucleotides that are from a nucleotide sequence derived from a nucleotide sequence represented by any of SEQ ID NOs: 1 to 165 and 635 to 642 by the replacement of u with t, or a complementary sequence thereof;
  2. (2) a polynucleotide comprising 15 or more consecutive nucleotides that are from a nucleotide sequence derived from a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 by the replacement of u with t, or a complementary sequence thereof; and
  3. (3) a polynucleotide comprising 15 or more consecutive nucleotides that are from a nucleotide sequence derived from a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 by the replacement of u with t, or a complementary sequence thereof.


[0501]  The polynucleotide is a polynucleotide consisting of a nucleotide sequence represented SEQ ID NO: 1, optionally together with any of SEQ ID NOs: 2 to 165 and 635 to 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a polynucleotide consisting of a complementary sequence thereof, a polynucleotide hybridizing under stringent conditions to any of these polynucleotides, or a variant thereof comprising 15 or more, preferably 17 or more, more preferably 19 or more consecutive nucleotides.

[0502] In a preferred embodiment, the invention may further include a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a polynucleotide consisting of a complementary sequence thereof, a polynucleotide hybridizing under stringent conditions to any of these polynucleotides, or a variant thereof comprising 15 or more, preferably 17 or more, more preferably 19 or more consecutive nucleotides.

[0503] In a preferred embodiment, the invention may further include a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a polynucleotide consisting of a complementary sequence thereof, a polynucleotide hybridizing under stringent conditions to any of these polynucleotides, or a variant thereof comprising 15 or more, preferably 17 or more, more preferably 19 or more consecutive nucleotides.

[0504] In a preferred embodiment, the fragment can be a polynucleotide comprising 15 or more, preferably 17 or more, more preferably 19 or more consecutive nucleotides.

[0505] In the present invention, the size of the polynucleotide fragment is the number of nucleotides in the range from, for example, 15 consecutive nucleotides to less than the total number of nucleotides of the sequence, from 17 consecutive nucleotides to less than the total number of nucleotides of the sequence, or from 19 consecutive nucleotides to less than the total number of nucleotides of the sequence, in the nucleotide sequence of each polynucleotide.

[0506]  Specific examples of the aforementioned polynucleotide combination as target nucleic acids for the kit or the device of the present invention can include combinations of the polynucleotides consisting of nucleotide sequences represented by SEQ ID NOs shown in Table 1 (SEQ ID NOs: 1 to 199 and 635 to 642 corresponding to the miRNA markers in Table 1).

[0507] The combination of the target nucleic acids for the kit or the device for discriminating a stomach cancer patient from a healthy subject according to the present invention is desirably, for example, a combination of SEQ ID NO: 1, optionally together with two or more other polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs shown in Table 1. Usually, a combination of two of these polynucleotides can produce adequate performance.

[0508] The specific combination of two polynucleotides consisting of the nucleotide sequences or the complementary sequences thereof for discriminating a stomach cancer patient from a healthy subject is preferably a combination comprising by SEQ ID NO: 1, optionally together with at least one or more of the newly found polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs 2 to 165 and 635 to 642, among the combinations of two of the aforementioned polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 199 and 635 to 642.

[0509] The number of the polynucleotides with cancer type specificity may be 2, 3, 4, 5, 6, 7, 8, 9, 10 or more in the combination and is more preferably 6 or more in the combination. Usually, the combination of 6 of these polynucleotides can produce adequate performance.

[0510] The kit or the device used in the present invention can also comprise a polynucleotide(s) that is already known or that will be found in the future, to enable detection of stomach cancer, in addition to the polynucleotide(s) (which may include a variant(s), a fragment(s), and a derivative(s)) as described above according to the present invention.

[0511] The kit of the present invention can also comprise an antibody for measuring a marker(s) for stomach cancer examination known in the art, such as CEA, or CA19-9, in addition to the polynucleotide(s) according to the present invention as described above, and a variant(s) thereof or a fragment(s) thereof.

[0512] These polynucleotides contained in the kit used in the present invention may be packaged in different containers either individually or in any combination.

[0513] The kit may comprise a kit for extracting a nucleic acid(s) (e.g., total RNA) from body fluids, cells, or tissues, a fluorescent material for labeling, an enzyme and a medium for nucleic acid amplification, an instruction manual, etc.

[0514] The device used in the present invention is a device for cancer marker measurement in which nucleic acids such as the polynucleotides according to the present invention described above are bonded or attached to, for example, a solid phase. Examples of the material for the solid phase include plastics, paper, glass, and silicon. The material for the solid phase is preferably a plastic from the viewpoint of easy processability. The solid phase has any shape and is, for example, square, round, reed-shaped, or film-shaped. The device of the present invention includes, for example, a device for measurement by a hybridization technique. Specific examples thereof include blotting devices and nucleic acid arrays (e.g., microarrays, DNA chips, and RNA chips).

[0515] The nucleic acid array technique is a technique which involves bonding or attaching the nucleic acids one by one by use of a method [e.g., a method of spotting the nucleic acids using a high-density dispenser called spotter or arrayer onto the surface of the solid phase surface-treated, if necessary, by coating with L-lysine or the introduction of a functional group such as an amino group or a carboxyl group, a method of spraying the nucleic acids onto the solid phase using an inkjet which injects very small liquid droplets by a piezoelectric element or the like from a nozzle, or a method of sequentially synthesizing nucleotides on the solid phase] to prepare an array such as a chip and measuring target nucleic acids through the use of hybridization using this array.

[0516] The kit or the device used in the present invention comprises nucleic acids capable of specifically binding to the polynucleotides of at least one or more, preferably at least two or more, more preferably at least three or more, most preferably at least five or more to all of the stomach cancer marker miRNAs, respectively, of the group 1 described above. The kit or the device of the present invention can optionally further comprise nucleic acids capable of specifically binding to the polynucleotides of at least one or more, preferably at least two or more, more preferably at least three or more, most preferably at least five or more to all of the stomach cancer marker miRNAs, respectively, of the group 2 described above. The kit or the device of the present invention can optionally further comprise nucleic acids capable of specifically binding to the polynucleotides of at least one or more, preferably at least two or more, more preferably at least three or more, most preferably at least five or more to all of the stomach cancer marker miRNAs, respectively, of the group 3 described above.

[0517] The kit or the device used in the present invention can be used for detecting stomach cancer as described in the Section 4 below.

4. Method for detecting stomach cancer



[0518] The present invention further provides a method for detecting stomach cancer, comprising using the kit or the device of the present invention (comprising the nucleic acid(s) that can be used in the present invention) described in the preceding Section 3 above to measure an expression level(s) of stomach cancer-derived gene: miR-4257, optionally together with one or more stomach cancer-derived gene(s) selected from the following group: miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 and miR-671-5p; and optionally an expression level(s) of stomach cancer-derived gene(s) selected from the following group: miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, and miR-486-3p; and optionally an expression level(s) of stomach cancer-derived gene(s) selected from the following group: miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 and miR-1199-5p in a sample in vitro, further comparing, for example, the expression level(s) of the gene(s) in the sample (e.g., blood, serum, or plasma) collected from a subject suspected of having stomach cancer with a control expression level in the sample collected from a healthy subject (including a non-stomach cancer patient), and evaluating the subject as having stomach cancer when the expression level of the target nucleic acid is statistically significantly different between the samples.

[0519] This method of the present invention enables a limitedly invasive, early diagnosis of cancer with high sensitivity and specificity and thereby brings about early treatment and improved prognosis. In addition, exacerbation of the disease or the effectiveness of surgical, radiotherapeutic, and chemotherapeutic treatments can be monitored.

[0520] The method for extracting the stomach cancer-derived gene(s) from the sample such as blood, serum, or plasma according to the present invention is particularly preferably prepared by the addition of a reagent for RNA extraction in 3D-Gene(™) RNA extraction reagent from liquid sample kit (Toray Industries, Inc.). A general acidic phenol method (acid guanidinium-phenolchloroform (AGPC)) may be used, or Trizol(™) (Life Technologies Corp.) may be used. The stomach cancer-derived gene(s) may be prepared by the addition of a reagent for RNA extraction containing acidic phenol, such as Trizol (Life Technologies Corp.) or Isogen (Nippon Gene Co., Ltd.). Alternatively, a kit such as miRNeasy(™) Mini Kit (Qiagen N.V.) may be used, though the method is not limited thereto.

[0521] The present invention also provides use of the kit or the device of the present invention for detecting in vitro an expression product(s) of a stomach cancer-derived miRNA gene(s) in a sample derived from a subject.

[0522] In the method of the present invention, the kit or the device described above comprises a single polynucleotide or any possible combination of polynucleotides that can be used in the present invention as described above.

[0523] In the detection or (genetic) diagnosis of stomach cancer according to the present invention, each polynucleotide contained in the kit or the device of the present invention can be used as a probe or a primer. In the case of using the polynucleotide as a primer, TaqMan(™) MicroRNA Assays from Life Technologies Corp., miScript PCR System from Qiagen N.V., or the like can be used, though the method is not limited thereto.

[0524] The polynucleotide contained in the kit or the device of the present invention can be used as a primer or a probe according to a routine method in a method known in the art for specifically detecting the particular gene, for example, a hybridization technique such as Northern blot, Southern blot, in situ hybridization, Northern hybridization, or Southern hybridization, or a quantitative amplification technique such as quantitative RT-PCR. A body fluid such as blood, serum, plasma, or urine from a subject is collected as a sample to be assayed according to the type of the detection method used. Alternatively, total RNA prepared from such a body fluid by the method described above may be used, and various polynucleotides including cDNA prepared on the basis of the RNA may be used.

[0525]  The kit or the device of the present invention is useful for the diagnosis of stomach cancer or the detection of the presence or absence of stomach cancer. Specifically, the detection of stomach cancer using the kit or the device can be performed by detecting in vitro an expression level(s) of a gene(s) using the nucleic acid probe(s) or the primer(s) contained in the kit or the device in a sample such as blood, serum, plasma, or urine from a subject suspected of having stomach cancer. The subject suspected of having stomach cancer can be evaluated as having stomach cancer when the expression level(s) of a target miRNA marker(s) measured using polynucleotide(s) (including a variant(s), a fragment(s), and a derivative(s) thereof) consisting of a nucleotide sequence(s) represented by SEQ ID NO: 1, optionally together with one or more of SEQ ID NOs: 2 to 165 and 635 to 642 or a complementary sequence(s) thereof, optionally a nucleotide sequence(s) represented by one or more of SEQ ID NOs: 166 to 169 or a complementary sequence(s) thereof, and optionally a nucleotide sequence(s) represented by one or more of SEQ ID NOs: 170 to 199 or a complementary sequence(s) thereof in the sample such as blood, serum, plasma, or urine of the subject is statistically significantly different from the expression level(s) thereof in the sample such as blood, serum, or plasma, or urine of a healthy subject.

[0526] The method of the present invention can be combined with gastric X-ray examination and gastroscopy as well as a diagnostic imaging method such as CT, PET, or MRI. The method of the present invention is capable of specifically detecting stomach cancer and can substantially discriminate stomach cancer from other cancers.

[0527] The method for detecting the absence of an expression product(s) of a stomach cancer-derived gene(s) or the presence of the expression product(s) of a stomach cancer-derived gene(s) in a sample using the kit or the device of the present invention comprises collecting a body fluid such as blood, serum, plasma, or urine of a subject, and measuring the expression level(s) of the target gene(s) contained therein using one or more polynucleotide(s) (including a variant(s), a fragment(s), and a derivative(s)) selected from the polynucleotide group of the present invention, to evaluate the presence or absence of stomach cancer or to detect stomach cancer. Using the method for detecting stomach cancer according to the present invention, for example, the presence or absence of amelioration of the disease or the degree of amelioration thereof in a stomach cancer patient to whom a therapeutic drug for the amelioration of the disease is administered can be also evaluated or diagnosed.

[0528] The method of the present invention can comprise, for example, the following steps (a), (b), and (c):
  1. (a) contacting a sample derived from a subject with a polynucleotide(s) in the kit or the device of the present invention in vitro;
  2. (b) measuring an expression level(s) of the target nucleic acid(s) in the sample using the polynucleotide(s) as a nucleic acid probe(s) or a primer(s); and
  3. (c) evaluating the presence or absence of stomach cancer (cells) in the subject on the basis of the result in the step (b).


[0529] Specifically, the present invention provides a method for detecting stomach cancer, comprising measuring an expression level(s) of a target nucleic acid(s) in a sample of a subject using a nucleic acid(s) capable of specifically binding to miR-4257, optionally together with at least one or more (preferably at least two or more) polynucleotide(s) selected from the group consisting of miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 and miR-671-5p and evaluating in vitro whether or not the subject has stomach cancer using the measured expression level(s) and a control expression level(s) of a healthy subject measured in the same way as above.

[0530] The term "evaluation" used herein is evaluation support based on results of in vitro examination, not physician's judgment.

[0531] As described above, as for the target nucleic acids in a preferred embodiment of the method of the present invention, specifically, miR-4257 is hsa-miR-4257, miR-6726-5p is hsa-miR-6726-5p, miR-1343-3p is hsa-miR-1343-3p, miR-1247-3p is hsa-miR-1247-3p, miR-6787-5p is hsa-miR-6787-5p, miR-6875-5p is hsa-miR-6875-5p, miR-1225-3p is hsa-miR-1225-3p, miR-8063 is hsa-miR-8063, miR-6781-5p is hsa-miR-6781-5p, miR-4746-3p is hsa-miR-4746-3p, miR-1908-5p is hsa-miR-1908-5p, miR-6756-5p is hsa-miR-6756-5p, miR-204-3p is hsa-miR-204-3p, miR-4651 is hsa-miR-4651, miR-6757-5p is hsa-miR-6757-5p, miR-6825-5p is hsa-miR-6825-5p, miR-7108-5p is hsa-miR-7108-5p, miR-4792 is hsa-miR-4792, miR-7641 is hsa-miR-7641, miR-3188 is hsa-miR-3188, miR-3131 is hsa-miR-3131, miR-6780b-5p is hsa-miR-6780b-5p, miR-8069 is hsa-miR-8069, miR-6840-3p is hsa-miR-6840-3p, miR-8072 is hsa-miR-8072, miR-1233-5p is hsa-miR-1233-5p, miR-6887-5p is hsa-miR-6887-5p, miR-1231 is hsa-miR-1231, miR-5572 is hsa-miR-5572, miR-6738-5p is hsa-miR-6738-5p, miR-6784-5p is hsa-miR-6784-5p, miR-6791-5p is hsa-miR-6791-5p, miR-6749-5p is hsa-miR-6749-5p, miR-6741-5p is hsa-miR-6741-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR-4419b is hsa-miR-4419b, miR-6746-5p is hsa-miR-6746-5p, miR-3184-5p is hsa-miR-3184-5p, miR-3679-5p is hsa-miR-3679-5p, miR-7110-5p is hsa-miR-7110-5p, miR-4516 is hsa-miR-4516, miR-6717-5p is hsa-miR-6717-5p, miR-6826-5p is hsa-miR-6826-5p, miR-4433b-3p is hsa-miR-4433b-3p, miR-3679-3p is hsa-miR-3679-3p, miR-3135b is hsa-miR-3135b, miR-3622a-5p is hsa-miR-3622a-5p, miR-711 is hsa-miR-711, miR-4467 is hsa-miR-4467, miR-6857-5p is hsa-miR-6857-5p, miR-6515-3p is hsa-miR-6515-3p, miR-1225-5p is hsa-miR-1225-5p, miR-187-5p is hsa-miR-187-5p, miR-3185 is hsa-miR-3185, miR-642b-3p is hsa-miR-642b-3p, miR-1249 is hsa-miR-1249, miR-744-5p is hsa-miR-744-5p, miR-4442 is hsa-miR-4442, miR-1228-3p is hsa-miR-1228-3p, miR-939-5p is hsa-miR-939-5p, miR-6845-5p is hsa-miR-6845-5p, miR-887-3p is hsa-miR-887-3p, miR-7845-5p is hsa-miR-7845-5p, miR-6729-5p is hsa-miR-6729-5p, miR-4632-5p is hsa-miR-4632-5p, miR-615-5p is hsa-miR-615-5p, miR-6724-5p is hsa-miR-6724-5p, miR-4728-5p is hsa-miR-4728-5p, miR-6732-5p is hsa-miR-6732-5p, miR-6816-5p is hsa-miR-6816-5p, miR-4695-5p is hsa-miR-4695-5p, miR-6088 is hsa-miR-6088, miR-7975 is hsa-miR-7975, miR-3197 is hsa-miR-3197, miR-6125 is hsa-miR-6125, miR-4433-3p is hsa-miR-4433-3p, miR-6727-5p is hsa-miR-6727-5p, miR-4706 is hsa-miR-4706, miR-7847-3p is hsa-miR-7847-3p, miR-6805-3p is hsa-miR-6805-3p, miR-6766-3p is hsa-miR-6766-3p, miR-1913 is hsa-miR-1913, miR-4649-5p is hsa-miR-4649-5p, miR-602 is hsa-miR-602, miR-3663-3p is hsa-miR-3663-3p, miR-6893-5p is hsa-miR-6893-5p, miR-6861-5p is hsa-miR-6861-5p, miR-4449 is hsa-miR-4449, miR-6842-5p is hsa-miR-6842-5p, miR-4454 is hsa-miR-4454, miR-5195-3p is hsa-miR-5195-3p, miR-663b is hsa-miR-663b, miR-6765-5p is hsa-miR-6765-5p, miR-4513 is hsa-miR-4513, miR-614 is hsa-miR-614, miR-6785-5p is hsa-miR-6785-5p, miR-6777-5p is hsa-miR-6777-5p, miR-940 is hsa-miR-940, miR-4741 is hsa-miR-4741, miR-6870-5p is hsa-miR-6870-5p, miR-6131 is hsa-miR-6131, miR-150-3p is hsa-miR-150-3p, miR-4707-5p is hsa-miR-4707-5p, miR-1915-3p is hsa-miR-1915-3p, miR-3937 is hsa-miR-3937, miR-937-5p is hsa-miR-937-5p, miR-4443 is hsa-miR-4443, miR-1914-3p is hsa-miR-1914-3p, miR-3620-5p is hsa-miR-3620-5p, miR-1268b is hsa-miR-1268b, miR-1227-5p is hsa-miR-1227-5p, miR-6880-5p is hsa-miR-6880-5p, miR-4417 is hsa-miR-4417, miR-6802-5p is hsa-miR-6802-5p, miR-6769a-5p is hsa-miR-6769a-5p, miR-663a is hsa-miR-663a, miR-6721-5p is hsa-miR-6721-5p, miR-4532 is hsa-miR-4532, miR-7977 is hsa-miR-7977, miR-92b-5p is hsa-miR-92b-5p, miR-371a-5p is hsa-miR-371a-5p, miR-6126 is hsa-miR-6126, miR-4734 is hsa-miR-4734, miR-4665-3p is hsa-miR-4665-3p, miR-423-5p is hsa-miR-423-5p, miR-1469 is hsa-miR-1469, miR-4675 is hsa-miR-4675, miR-1915-5p is hsa-miR-1915-5p, miR-6716-5p is hsa-miR-6716-5p, miR-718 is hsa-miR-718, miR-4281 is hsa-miR-4281, miR-6820-5p is hsa-miR-6820-5p, miR-6795-5p is hsa-miR-6795-5p, miR-6779-5p is hsa-miR-6779-5p, miR-7109-5p is hsa-miR-7109-5p, miR-6798-5p is hsa-miR-6798-5p, miR-4648 is hsa-miR-4648, miR-8059 is hsa-miR-8059, miR-6765-3p is hsa-miR-6765-3p, miR-6132 is hsa-miR-6132, miR-4492 is hsa-miR-4492, miR-7107-5p is hsa-miR-7107-5p, miR-3195 is hsa-miR-3195, miR-3180 is hsa-miR-3180, miR-296-3p is hsa-miR-296-3p, miR-564 is hsa-miR-564, miR-1268a is hsa-miR-1268a, miR-6848-5p is hsa-miR-6848-5p, miR-762 is hsa-miR-762, miR-2861 is hsa-miR-2861, miR-1203 is hsa-miR-1203, miR-1260b is hsa-miR-1260b, miR-4476 is hsa-miR-4476, miR-6885-5p is hsa-miR-6885-5p, miR-6769b-5p is hsa-miR-6769b-5p, miR-23b-3p is hsa-miR-23b-3p, miR-1343-5p is hsa-miR-1343-5p, miR-3621 is hsa-miR-3621, miR-4688 is hsa-miR-4688, miR-4286 is hsa-miR-4286, miR-4640-5p is hsa-miR-4640-5p, miR-4739 is hsa-miR-4739, miR-1260a is hsa-miR-1260a, miR-4276 is hsa-miR-4276, miR-7106-5p is hsa-miR-7106-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6774-5p is hsa-miR-6774-5p, miR-4707-3p is hsa-miR-4707-3p, miR-4534 is hsa-miR-4534, miR-4294 is hsa-miR-4294, miR-6850-5p is hsa-miR-6850-5p, miR-6089 is hsa-miR-6089, and miR-671-5p is hsa-miR-671-5p.

[0532] In a preferred embodiment of the method of the present invention, specifically, the nucleic acid(s) (specifically, probe(s) or primer(s)) is selected from the group consisting of the following polynucleotides (a) to (e):
  1. (a) a polynucleotide consisting of a nucleotide sequence represented by SEQ ID NO: 1, optionally together with any of SEQ ID NO: 2 to 165 and 635 to 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,
  2. (b) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NO: 1 , optionally together with any of SEQ ID NO: 2 to 165 and 635 to 642,
  3. (c) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NO: 1, optionally together with any of SEQ ID NO: 2 to 165 and 635 to 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,
  4. (d) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NO: 1, optionally together with any of SEQ ID NO: 2 to 165 and 635 to 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, and
  5. (e) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a) to (d).


[0533] The method of the present invention can further employ a nucleic acid(s) capable of specifically binding to at least one or more polynucleotides selected from miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, and miR-486-3p.

[0534] In a preferred embodiment, as for such a nucleic acid, specifically, miR-128-2-5p is hsa-miR-128-2-5p, miR-125a-3p is hsa-miR-125a-3p, miR-92a-2-5p is hsa-miR-92a-2-5p, and miR-486-3p is hsa-miR-486-3p.

[0535] In a preferred embodiment, such a nucleic acid(s) is specifically selected from the group consisting of the following polynucleotides (f) to (j):

(f) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(g) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169,

(h) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(i) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, and

(j) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (f) to (i).



[0536] The method of the present invention can further employ a nucleic acid(s) capable of specifically binding to at least one or more polynucleotides selected from the group consisting of miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141, and miR-1199-5p.

[0537] In a preferred embodiment, as for such a nucleic acid, specifically, miR-3196 is hsa-miR-3196, miR-211-3p is hsa-miR-211-3p, miR-4271 is hsa-miR-4271, miR-6851-5p is hsa-miR-6851-5p, miR-149-3p is hsa-miR-149-3p, miR-4667-5p is hsa-miR-4667-5p, miR-135a-3p is hsa-miR-135a-3p, miR-4486 is hsa-miR-4486, miR-4697-5p is hsa-miR-4697-5p, miR-4725-3p is hsa-miR-4725-3p, miR-6510-5p is hsa-miR-6510-5p, miR-5001-5p is hsa-miR-5001-5p, miR-4673 is hsa-miR-4673, miR-4466 is hsa-miR-4466, miR-23a-3p is hsa-miR-23a-3p, miR-3656 is hsa-miR-3656, miR-6782-5p is hsa-miR-6782-5p, miR-4689 is hsa-miR-4689, miR-451a is hsa-miR-451a, miR-4446-3p is hsa-miR-4446-3p, miR-3180-3p is hsa-miR-3180-3p, miR-642a-3p is hsa-miR-642a-3p, miR-6889-5p is hsa-miR-6889-5p, miR-3178 is hsa-miR-3178, miR-4665-5p is hsa-miR-4665-5p, miR-6722-3p is hsa-miR-6722-3p, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-4507 is hsa-miR-4507, miR-3141 is hsa-miR-3141, and miR-1199-5p is hsa-miR-1199-5p.

[0538] Specifically, the nucleic acid(s) further used is a polynucleotide(s) selected from the group consisting of the following polynucleotides (k) to (o):

(k) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(1) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199,

(m) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(n) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, and

(o) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (k) to (n).



[0539] Examples of the sample used in the method of the present invention can include samples prepared from a living tissue (preferably a stomach tissue) or a body fluid such as blood, serum, plasma, or urine from the subject. Specifically, for example, an RNA-containing sample prepared from the tissue, a polynucleotide-containing sample further prepared therefrom, a body fluid such as blood, serum, plasma, or urine, a portion or the whole of a living tissue collected from the subject by biopsy or the like, or a living tissue excised by surgery can be used, and the sample for measurement can be prepared therefrom.

[0540] The subject used herein refers to a mammal, for example, a human, a monkey, a mouse or a rat without any limitation, and is preferably a human.

[0541] The steps of the method of the present invention can be changed according to the type of the sample to be assayed.

[0542] In the case of using RNA as an analyte, the detection of stomach cancer (cells) can comprise, for example, the following steps (a), (b), and (c):
  1. (a) binding RNA(s) prepared from the sample of the subject or a complementary polynucleotide(s) (cDNA(s)) transcribed therefrom to a polynucleotide(s) in the kit or the device of the present invention;
  2. (b) measuring the sample-derived RNA or the cDNA(s) synthesized from the RNA, bound with the polynucleotide by hybridization using the polynucleotide as a nucleic acid probe(s) or by quantitative RT-PCR using the polynucleotide(s) as a primer(s); and
  3. (c) evaluating the presence or absence of stomach cancer (or stomach cancer-derived gene expression) on the basis of the measurement results of the step (b).


[0543]  For example, various hybridization methods can be used for detecting, examining, evaluating, or diagnosing stomach cancer (or stomach cancer-derived gene expression) in vitro according to the present invention. For example, Northern blot, Southern blot, RT-PCR, DNA chip analysis, in situ hybridization, Northern hybridization, or Southern hybridization can be used as such a hybridization method.

[0544] In the case of using the Northern blot, the presence or absence of expression of each gene or the expression level thereof in the RNA can be detected or measured by use of the nucleic acid probe(s) that can be used in the present invention. Specific examples thereof can include a method which comprises labeling the nucleic acid probe (or a complementary strand) with a radioisotope (32P, 33P, 35S, etc.), a fluorescent material, or the like, hybridizing the labeled product with the tissue-derived RNA of the subject, which is transferred to a nylon membrane or the like according to a routine method, and then detecting and measuring a signal derived from the label (radioisotope or fluorescent material) on the formed DNA/RNA duplex using a radiation detector (examples thereof can include BAS-1800 II (Fujifilm Corp.)) or a fluorescence detector (examples thereof can include STORM 865 (GE Healthcare Japan Corp.)).

[0545] In the case of using the quantitative RT-PCR, the presence or absence of expression of each gene or the expression level thereof in the RNA can be detected or measured by use of the primer that can be used in the present invention. Specific examples thereof can include a method which comprises preparing cDNA from the tissue-derived RNA of the subject according to a routine method, hybridizing a pair of primers (consisting of a plus strand and a reverse strand binding to the cDNA) of the present invention with the cDNA such that the region of each target gene can be amplified with the cDNA as a template, and performing PCR according to a routine method to detect the obtained double-stranded DNA. The method for detecting the double-stranded DNA can include a method of performing the PCR using the primers labeled in advance with a radioisotope or a fluorescent material, a method of electrophoresing the PCR product on an agarose gel and staining the double-stranded DNA with ethidium bromide or the like for detection, and a method of transferring the produced double-stranded DNA to a nylon membrane or the like according to a routine method and hybridizing the double-stranded DNA to a labeled nucleic acid probe for detection.

[0546] In the case of using the nucleic acid array analysis, an RNA chip or a DNA chip in which the nucleic acid probes (single-stranded or double-stranded) of the present invention is attached to a substrate (solid phase) is used. Regions having the attached nucleic acid probes are referred to as probe spots, and regions having no attached nucleic acid probe are referred to as blank spots. A group of genes immobilized on a solid-phase substrate is generally called a nucleic acid chip, a nucleic acid array, a microarray, or the like. The DNA or RNA array includes a DNA or RNA macroarray and a DNA or RNA microarray. The term "chip" used herein includes these arrays. 3D-Gene(™) Human miRNA Oligo chip (Toray Industries, Inc.) can be used as the DNA chip, though the DNA chip is not limited thereto.

[0547] Examples of the measurement using the DNA chip can include, but are not limited to, a method of detecting and measuring a signal derived from the label on nucleic acid probes using an image detector (examples thereof can include Typhoon 9410 (GE Healthcare) and 3D-Gene(™) scanner (Toray Industries, Inc.)).

[0548] The "stringent conditions" used herein are, as mentioned above, conditions under which a nucleic acid probe hybridizes to its target sequence to a larger extent (e.g., a measurement value equal to or larger than "(a mean of background measurement values) + (a standard deviation of the background measurement values) × 2") than that for other sequences.

[0549] The stringent conditions are defined by hybridization and subsequent washing conditions. Examples of the hybridization conditions include, but not limited to, 30°C to 60°C for 1 to 24 hours in a solution containing SSC, a surfactant, formamide, dextran sulfate, a blocking agent(s), etc. In this context, 1 × SSC is an aqueous solution (pH 7.0) containing 150 mM sodium chloride and 15 mM sodium citrate. The surfactant includes, for example, SDS (sodium dodecyl sulfate), Triton, or Tween. The hybridization conditions more preferably involve 3 to 10 × SSC and 0.1 to 1% SDS. Examples of the conditions for the washing, following the hybridization, which is another condition to define the stringent conditions, can include conditions involving continuous washing at 30°C in a solution containing 0.5 × SSC and 0.1% SDS, at 30°C in a solution containing 0.2 × SSC and 0.1% SDS, and at 30°C in a 0.05 × SSC solution. It is desirable that the complementary strand should maintain its hybridized state with a target plus strand even by washing under such conditions. Specifically, examples of such a complementary strand can include a strand consisting of a nucleotide sequence in a completely complementary relationship with the nucleotide sequence of the target plus strand, and a strand consisting of a nucleotide sequence having at least 80%, preferably at least 85%, more preferably at least 90% or at least 95%, for example, at least 98% or at least 99% identity to the strand.

[0550] Other examples of the "stringent conditions" for the hybridization are described in, for example, Sambrook, J. & Russel, D., Molecular Cloning, A LABORATORY MANUAL, Cold Spring Harbor Laboratory Press, published on January 15, 2001, Vol. 1, 7.42 to 7.45 and Vol. 2, 8.9 to 8.17, and can be used in the present invention.

[0551] Examples of the conditions for carrying out PCR using a polynucleotide fragment(s) in the kit of the present invention as a primer(s) include treatment for approximately 15 seconds to 1 minute at 5 to 10°C plus a Tm value calculated from the sequence(s) of the primer(s), using a PCR buffer having composition such as 10 mM Tris-HCL (pH 8.3), 50 mM KCL, and 1 to 2 mM MgCl2. Examples of the method for calculating such a Tm value include Tm value = 2 × (the number of adenine residues + the number of thymine residues) + 4 × (the number of guanine residues + the number of cytosine residues).

[0552] In the case of using the quantitative RT-PCR, a commercially available kit for measurement specially designed for quantitatively measuring miRNA, such as TaqMan(™) MicroRNA Assays (Life Technologies Corp.); LNA(™)-based MicroRNA PCR (Exiqon); or Ncode(™) miRNA qRT-PCT kit (Invitrogen Corp.) may be used.

[0553] For the calculation of gene expression levels according to the present invention, statistical treatment described in, for example, Statistical analysis of gene expression microarray data (Speed T., Chapman and Hall/CRC), and A beginner's guide Microarray gene expression data analysis (Causton H.C. et al., Blackwell publishing) can be used, though the calculation method is not limited thereto. For example, twice, preferably 3 times, more preferably 6 times the standard deviation of the measurement values of the blank spots are added to the average measurement value of the blank spots on the DNA chip, and probe spots having a signal value equal to or larger than the resulting value can be regarded as detection spots. Alternatively, the average measurement value of the blank spots is regarded as a background and can be subtracted from the measurement values of the probe spots to determine gene expression levels. A missing value for a gene expression level can be excluded from the analyte, preferably replaced with the smallest value of the gene expression level in each DNA chip, or more preferably replaced with a value obtained by subtracting 0.1 from a logarithmic value of the smallest value of the gene expression level. In order to eliminate low-signal genes, only a gene having a gene expression level of 26, preferably 28, more preferably 210 or larger in 20% or more, preferably 50% or more, more preferably 80% or more of the number of measurement samples can be selected as the analyte. Examples of the normalization of the gene expression level include, but are not limited to, global normalization and quantile normalization (Bolstad, B. M. et al., 2003, Bioinformatics, Vol. 19, p. 185-193).

[0554] The present invention also provides a method comprising measuring a target gene or gene expression level(s) in a sample derived from a subject using the polynucleotide(s), the kit, or the device (e.g., chip) for detection of the present invention, or a combination thereof, preparing a discriminant (discriminant function) with gene expression levels in a sample derived from a stomach cancer patient and a sample derived from a healthy subject as supervising samples, and determining or evaluating the presence and/or absence of the stomach cancer-derived gene(s) in the sample.

[0555] Specifically, the present invention further provides the method comprising: a first step of measuring in vitro an expression level(s) of a target gene(s) (target nucleic acid) in multiple samples that were known to be able to determine or evaluate the presence and/or absence of the stomach cancer-derived gene(s) in the samples, using the polynucleotide(s), the kit, or the device (e.g., chip) for detection of the present invention, or a combination thereof; a second step of constructing a discriminant with the measurement values of the expression level(s) of the target gene(s) that was obtained in the first step as supervising samples; a third step of measuring in vitro an expression level(s) of the target gene(s) in a sample derived from a subject in the same way as in the first step; and a fourth step of substituting the measurement value(s) of the expression level(s) of the target gene(s) obtained in the third step into the discriminant obtained in the second step, and determining or evaluating the presence or absence of the stomach cancer-derived gene(s) in the sample on the basis of the results obtained from the discriminant, wherein the target gene(s) can be detected using the polynucleotide(s) or using a polynucleotide(s) for the detection, that was contained in the polynucleotide, the kit or the device (e.g., chip). In this context, the discriminant can be prepared by use of Fisher's discriminant analysis, nonlinear discriminant analysis based on Mahalanobis' distance, neural network, Support Vector Machine (SVM), or the like, though the method is not limited thereto.

[0556] When a clustering boundary is a straight line or a hyperplane, the linear discriminant analysis is a method for determining the association of a cluster using Formula 1 as a discriminant. In Formula 1, x represents an explanatory variable, w represents a coefficient of the explanatory variable, and w0 represents a constant term.



[0557] Values obtained from the discriminant are referred to as discriminant scores. The measurement values of a newly offered data set can be substituted as explanatory variables into the discriminant to determine clusters on the basis of the signs of the discriminant scores.

[0558] The Fisher's discriminant analysis, one type of linear discriminant analysis, is a dimension reduction method for selecting a dimension suitable for discriminating classes, and constructs a highly discriminating synthetic variable by focusing on the variance of the synthetic variables and minimizing the variance of data having the same label (Venables, W.N. et al., Modern Applied Statistics with S. Fourth edition. Springer., 2002). In the Fisher's discriminant analysis, direction w of projection is determined so as to maximize Formula 2. In Formula 2, µ represents an average input, ng represents the number of data associate with class g, and µg represents an average input of the data associate with class g. The numerator and the denominator are the interclass variance and the intraclass variance, respectively, when each data is projected in the direction of the vector w. Discriminant coefficient wi is determined by maximizing this ratio (Takafumi Kanamori et al., "Pattern Recognition", Kyoritsu Shuppan Co., Ltd. (2009); and Richard O. et al., Pattern Classification Second Edition., Wiley-Interscience, 2000).

subject to



[0559] The Mahalanobis' distance is calculated according to Formula 3 in consideration of data correlation and can be used as nonlinear discriminant analysis for determining a cluster in which a data point belongs to, based on a short Mahalanobis' distance from the data point to that cluster. In Formula 3, µ represents a central vector of each cluster, and S-1 represents an inverse matrix of the variance-covariance matrix of the cluster. The central vector is calculated from explanatory variable x, and an average vector, a median value vector, or the like can be used.



[0560] SVM is a discriminant analysis method devised by V. Vapnik (The Nature of Statistical Leaning Theory, Springer, 1995). Particular data points of a data set having known classes are defined as explanatory variables, and classes are defined as objective variables. A boundary plane called hyperplane for correctly classifying the data set into the known classes is determined, and a discriminant for data classification is determined using the boundary plane. Then, the measurement values of a newly offered data set can be substituted as explanatory variables into the discriminant to determine classes. In this respect, the result of the discriminant analysis may be classes, may be a probability of data to be classified into correct classes, or may be the distance from the hyperplane. In SVM, a method of nonlinearly converting a feature vector to a high dimension and performing linear discriminant analysis in the space is known as a method for tackling nonlinear problems. An expression in which an inner product of two factors in a nonlinearly mapped space is expressed only by inputs in their original spaces is called kernel. Examples of the kernel can include a linear kernel, a RBF (Radial Basis Function) kernel, and a Gaussian kernel. While highly dimensional mapping is performed according to the kernel, the optimum discriminant, i.e., a discriminant, can be actually constructed by mere calculation according to the kernel, which avoids calculating features in the mapped space (e.g., Hideki Aso et al., Frontier of Statistical Science 6 "Statistics of pattern recognition and learning - New concepts and approaches", Iwanami Shoten, Publishers (2004); Nello Cristianini et al., Introduction to SVM, Kyoritsu Shuppan Co., Ltd. (2008)).

[0561] C-support vector classification (C-SVC), one type of SVM, comprises preparing a hyperplane by supervising a data set with the explanatory variables of two groups and classifying an unknown data set into either of the groups (C. Cortes et al., 1995, Machine Learning, Vol. 20, p. 273-297).

[0562] Exemplary calculation of the C-SVC discriminant that can be used in the method of the present invention will be given below. First, all subjects are divided into two groups, i.e., a stomach cancer patient group and a healthy subject group. For example, stomach tissue examination can be used for each subject to be confirmed either as a stomach cancer patient or a healthy subject.

[0563] Next, a data set consisting of comprehensive gene expression levels of serum-derived samples of the two divided groups (hereinafter, this data set is referred to as a training cohort) is prepared, and a C-SVC discriminant is determined by using genes that were found to differ clearly in their gene expression levels between the two groups as explanatory variables and using this grouping as objective variables (e.g., -1 and +1). An optimizing objective function is represented by Formula 4 wherein e represents all input vectors, y represents an objective variable, a represents a Lagrange's undetermined multiplier vector, Q represents a positive definite matrix, and C represents a parameter for adjusting constrained conditions.

subject to



[0564] Formula 5 is a finally obtained discriminant, and a group in which the data point belongs to can be determined on the basis of the sign of a value obtained according to the discriminant. In this formula, x represents a support vector, y represents a label indicating the association of a group, a represents the corresponding coefficient, b represents a constant term, and K represents a kernel function.



[0565] For example, a RBF kernel defined by Formula 6 can be used as the kernel function. In this formula, x represents a support vector, and γ represents a kernel parameter for adjusting the complexity of the hyperplane.



[0566] In addition, an approach such as neural network, k-nearest neighbor algorithms, decision trees, or logistic regression analysis can be selected as a method for determining or evaluating the presence and/or absence of expression of a stomach cancer-derived target gene(s) in a sample derived from a subject, or for evaluating the expression level thereof by comparison with a control derived from a healthy subject.

[0567] The method of the present invention can comprise, for example, the following steps (a), (b), and (c):
  1. (a) measuring an expression level(s) of a target gene(s) in tissues containing stomach cancer-derived genes derived from stomach cancer patients and/or samples already known to be tissues containing no stomach cancer-derived gene(s) derived from healthy subjects, using the polynucleotide(s), the kit, or the device (e.g., DNA chip) for detection according to the present invention;
  2. (b) preparing the discriminants of Formulas 1 to 3, 5, and 6 described above from the measurement values of the expression level measured in the step (a); and
  3. (c) measuring an expression level(s) of the target gene(s) in a sample derived from a subject using the polynucleotide(s), the kit, or the device (e.g., DNA chip) for diagnosis (detection) according to the present invention, substituting the obtained measurement value(s) into the discriminants prepared in the step (b), and determining or evaluating the presence and/or absence of the stomach cancer-derived target gene(s) in the sample, or evaluating the expression level(s) thereof by comparison with a healthy subject-derived control, on the basis of the obtained results. In this context, in the discriminants of Formulas 1 to 3, 5, and 6, x represents an explanatory variable and includes a value obtained by measuring a polynucleotide(s) selected from the polynucleotides described in the Section 2 above, or any fragment thereof, etc. Specifically, the explanatory variable for discriminating a stomach cancer patient from a healthy subject according to the present invention is a gene expression level(s) selected from, for example, the following expression levels (1) to (3):
    1. (1) a gene expression level(s) in the serum of a stomach cancer patient or a healthy subject measured by any DNA comprising 15 or more consecutive nucleotides in a nucleotide sequence represented by SEQ ID NO: 1, optionally together with any of SEQ ID NOs 2 to 165 and 635 to 642 or a complementary sequence thereof,
    2. (2) a gene expression level(s) in the serum of a stomach cancer patient or a healthy subject measured by any DNA comprising 15 or more consecutive nucleotides in a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a complementary sequence thereof, and
    3. (3) a gene expression level(s) in the serum of a stomach cancer patient or a healthy subject measured by any DNA comprising 15 or more consecutive nucleotides in a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a complementary sequence thereof.


[0568] As described above, for the method for determining or evaluating the presence and/or absence of a stomach cancer-derived gene(s) in a sample derived from a subject, the preparation of a discriminant requires a discriminant prepared in a training cohort. For enhancing the accuracy of the discriminant, it is necessary for the discriminant to use genes that show clear difference between two groups in the training cohort.

[0569] Each gene that is used for an explanatory variable in a discriminant is preferably determined as follows. First, comprehensive gene expression levels of a stomach cancer patient group and comprehensive gene expression levels of a healthy subject group in a training cohort are used as a data set, the degree of difference in the expression level of each gene between the two groups is determined through the use of, for example, the P value of t test, which is parametric analysis, or the P value of Mann-Whitney's U test or Wilcoxon test, which is nonparametric analysis.

[0570] The gene can be regarded as being statistically significant when the critical rate (significance level) as the P value obtained by the test is smaller than, for example, 5%, 1%, or 0.01%.

[0571] In order to correct an increased probability of type I error attributed to the repetition of a test, a method known in the art, for example, Bonferroni or Holm method, can be used for the correction (e.g., Yasushi Nagata et al., "Basics of statistical multiple comparison methods", Scientist Press Co., Ltd. (2007)). As an example of the Bonferroni correction, for example, the P value obtained by a test is multiplied by the number of repetitions of the test, i.e., the number of genes used in the analysis, and the obtained value can be compared with a desired significance level to suppress a probability of causing type I error in the whole test.

[0572] Instead of the statistical test, the absolute value (fold change) of an expression ratio of a median value of each gene expression level between gene expression levels of a stomach cancer patient group and gene expression levels of a healthy subject group may be calculated to select a gene that is used for an explanatory variable in a discriminant. Alternatively, ROC curves may be prepared using gene expression levels of a stomach cancer patient group and a healthy subject group, and a gene that is used for an explanatory variable in a discriminant can be selected on the basis of an AUROC value.

[0573] Next, a discriminant that can be calculated by various methods described above is prepared using any number of genes having large difference in their gene expression levels determined here. Examples of the method for constructing a discriminant that produces the largest discriminant accuracy include a method of constructing a discriminant in every combination of genes that satisfy the significance level of P value, and a method of repetitively evaluating a discriminant while increasing the number of genes for use one by one in a descending order of difference in gene expression level (Furey TS. et al., 2000, Bioinformatics., Vol. 16, p. 906-14). A gene expression level of another independent stomach cancer patient or healthy subject is substituted as an explanatory variable into this discriminant to calculate discriminant results of the group to which this independent stomach cancer patient or healthy subject associate. Specifically, the found gene set for diagnosis and the discriminant constructed using the gene set for diagnosis can be evaluated in an independent sample cohort to find a more universal gene set for diagnosis capable of detecting stomach cancer and a more universal method for discriminating stomach cancer.

[0574] Split-sample method is preferably used for evaluating the discriminant performance (generality) of the discriminant. Specifically, a data set is divided into a training cohort and a validation cohort, and gene selection by a statistical test and discriminant preparation are performed in the training cohort. Accuracy, sensitivity, and specificity are calculated using a result of discriminating a validation cohort according to the discriminant and a true group to which the validation cohort associate, to evaluate the performance of the discriminant. On the other hand, instead of dividing a data set, the gene selection by a statistical test and discriminant preparation may be performed using all of samples, and accuracy, sensitivity, and specificity can be calculated by the discriminant analysis of a newly prepared samples for evaluation of the performance of the discriminant.

[0575] The present invention provides a polynucleotide(s) for detection or for disease diagnosis useful in the diagnosis and treatment of stomach cancer, a method for detecting stomach cancer using the polynucleotide(s), and a kit and a device for the detection of stomach cancer, comprising the polynucleotide(s). Particularly, in order to select a gene(s) for diagnosis and prepare a discriminant so as to exhibit accuracy beyond a stomach cancer diagnosis method using existing tumor markers CEA and CA19-9, a gene set for diagnosis and a discriminant for the method of the present invention, that exhibit accuracy beyond CEA and CA19-9, can be constructed, for example, by comparing expressed genes in serum derived from a patient confirmed to be negative using CEA and CA19-9 but finally found to have stomach cancer by detailed examination such as computed tomography using a contrast medium, with genes expressed in serum derived from a patient having no stomach cancer.

[0576] For example, the gene set for diagnosis is set to any combination selected from one or two or more of the polynucleotides based on a nucleotide sequence(s) represented SEQ ID NO: 1, optionally together with any of SEQ ID NOs: 2 to 165 and 635 to 642 or a complementary sequence(s) thereof as described above; and optionally one or two or more of the polynucleotides based on a nucleotide sequence(s) represented by any of SEQ ID NOs: 166 to 169 or a complementary sequence(s) thereof; and optionally one or two or more of the polynucleotides based on a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a complementary sequence thereof. Further, a discriminant is constructed using expression levels of the gene set for diagnosis in samples derived from class I stomach cancer patients and samples derived from class II healthy subjects as a result of tissue diagnosis. As a result, the presence or absence of stomach cancer-derived genes in an unknown sample can be determined with 100% accuracy at the maximum by measuring expression levels of the gene set for diagnosis in an unknown sample.

Examples



[0577] Hereinafter, the present invention will be described further specifically with reference to Examples below. However, the scope of the present invention is not intended to be limited by these Examples.

[Reference Example 1]


<Collection of samples from stomach cancer patient and healthy subject>



[0578] Serum was collected using VENOJECT II vacuum blood collecting tube VP-AS109K60 (Terumo Corp.) from each of 100 healthy subjects and 34 stomach cancer patients (19 cases with stage IA, 5 cases with stage IB, 2 cases with stage IIA, 2 cases with stage IIB, 3 cases with stage IIIA, and 3 cases with stage IIIC) with no primary cancer found in areas other than stomach cancer after acquisition of informed consent, and used as a training cohort. Likewise, serum was collected using VENOJECT II vacuum blood collecting tube VP-AS109K60 (Terumo Corp.) from each of 50 healthy subjects and 16 stomach cancer patients (9 cases with stage IA, 2 cases with stage IB, 2 cases with stage IIA, 1 case with stage IIB, 1 case with stage IIIA, and 1 case with stage IIIC) with no primary cancer found in areas other than stomach cancer after acquisition of informed consent, and used as a validation cohort.

<Extraction of total RNA>



[0579] Total RNA was obtained from 300 µL of the serum sample obtained from each of 200 persons in total of 150 healthy subjects and 50 stomach cancer patients included in the training cohort and the validation cohort, using a reagent for RNA extraction in 3D-Gene(™) RNA extraction reagent from liquid sample kit (Toray Industries, Inc.) according to the protocol provided by the manufacturer.

<Measurement of gene expression level>



[0580] miRNAs in the total RNA obtained from the serum samples of each of 200 persons in total of 150 healthy subjects and 50 stomach cancer patients included in the training cohort and the validation cohort were fluorescently labeled using 3D-Gene(™) miRNA Labeling kit (Toray Industries, Inc.) according to the protocol (ver 2.20) provided by the manufacturer. The oligo DNA chip used was 3D-Gene(™) Human miRNA Oligo chip (Toray Industries, Inc.) with attached probes having sequences complementary to 2,555 miRNAs among the miRNAs registered in miRBase Release 20. Hybridization between the miRNAs in the total RNA and the probes on the DNA chip under stringent conditions and washing following the hybridization were performed according to the protocol provided by the manufacturer. The DNA chip was scanned using 3D-Gene(™) scanner (Toray Industries, Inc.) to obtain images. Fluorescence intensity was digitized using 3D-Gene(™) Extraction (Toray Industries, Inc.). The digitized fluorescence intensity was converted to a logarithmic value having a base of 2 and used as a gene expression level, from which a blank value was subtracted. A missing value was replaced with a value obtained by subtracting 0.1 from a logarithmic value of the smallest value of the gene expression level in each DNA chip. As a result, the comprehensive gene expression levels of the miRNAs in the sera were obtained in the 50 stomach cancer patients and the 150 healthy subjects. Calculation and statistical analysis using the digitized gene expression levels of the miRNAs were carried out using R language 3.0.2 (R Development Core Team (2013). R: A language and environment for statistical computing. R Foundation for Statistical Computing, URL http://www.R-project.org/) and MASS package 7.3-30 (Venables, W. N. & Ripley, B. D. (2002) Modern Applied Statistics with S. Fourth Edition. Springer, New York. ISBN 0-387-95457-0).

[Reference Example 2]


<Collection of sample from patient with cancer other than stomach cancers>



[0581] Serum was collected using VENOJECT II vacuum blood collecting tube VP-AS109K60 (Terumo Corp.) from each of 63 pancreatic cancer patients, 65 bile duct cancer patients, 35 colorectal cancer patients, 32 liver cancer patients, and 17 benign pancreaticobiliary disease patients with no cancer found in other organs after acquisition of informed consent, and used as a training cohort together with the samples of 34 stomach cancer patients and 102 healthy subjects of Reference Example 1. Likewise, serum was collected using VENOJECT II vacuum blood collecting tube VP-AS109K60 (Terumo Corp.) from each of 37 pancreatic cancer patients, 33 bile duct cancer patients, 15 colorectal cancer patients, 20 liver cancer patients, and 4 benign pancreaticobiliary disease patients with no cancer found in other organs after acquisition of informed consent, and used as a validation cohort together with the samples of 16 stomach cancer patients with no cancer found in areas other than stomach cancer and 48 healthy subjects of Reference Example 1. Subsequent operations were conducted in the same way as in Reference Example 1.

[Example 1]


<Selection of gene markers using the training cohort, and method for evaluating stomach cancer discriminant performance of single gene marker using the validation cohort>



[0582] In this Example, a gene marker for discriminating a stomach cancer patient from a healthy subject was selected from the training cohort and studied in samples of the validation cohort independent of the training cohort, for a method for evaluating the stomach cancer discriminant performance of each selected gene marker alone.

[0583] Specifically, first, the miRNA expression levels of the training cohort and the validation cohort obtained in the preceding Reference Examples were combined and normalized by quantile normalization.

[0584]  Next, genes for diagnosis were selected using the training cohort. Here, in order to acquire diagnostic markers with higher reliability, only genes having the expression level of 26 or higher in 50% or more of the samples in either of the stomach cancer patient group of the training cohort or the healthy subject group of the training cohort were selected. In order to further acquire statistically significant genes for discriminating a stomach cancer patient group from a healthy subject group, the P value obtained by two-tailed t-test assuming equal variance as to each gene expression level was corrected by the Bonferroni method, and genes that satisfied p < 0.01 were acquired as gene markers for use in explanatory variables of a discriminant. The result is described in Table 2.

[0585] In this way, polynucleotides consisting of hsa-miR-4257, hsa-miR-6726-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-6787-5p, hsa-miR-6875-5p, hsa-miR-1225-3p, hsa-miR-8063, hsa-miR-6781-5p, hsa-miR-4746-3p, hsa-miR-1908-5p, hsa-miR-6756-5p, hsa-miR-204-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-6825-5p, hsa-miR-7108-5p, hsa-miR-4792, hsa-miR-7641, hsa-miR-3188, hsa-miR-3131, hsa-miR-6780b-5p, hsa-miR-8069, hsa-miR-6840-3p, hsa-miR-8072, hsa-miR-1233-5p, hsa-miR-6887-5p, hsa-miR-1231, hsa-miR-5572, hsa-miR-6738-5p, hsa-miR-6784-5p, hsa-miR-6791-5p, hsa-miR-6749-5p, hsa-miR-6741-5p, hsa-miR-128-1-5p, hsa-miR-4419b, hsa-miR-6746-5p, hsa-miR-3184-5p, hsa-miR-3679-5p, hsa-miR-7110-5p, hsa-miR-4516, hsa-miR-6717-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-3679-3p, hsa-miR-3135b, hsa-miR-3622a-5p, hsa-miR-711, hsa-miR-4467, hsa-miR-6857-5p, hsa-miR-6515-3p, hsa-miR-1225-5p, hsa-miR-187-5p, hsa-miR-3185, hsa-miR-642b-3p, hsa-miR-1249, hsa-miR-744-5p, hsa-miR-4442, hsa-miR-1228-3p, hsa-miR-939-5p, hsa-miR-6845-5p, hsa-miR-887-3p, hsa-miR-7845-5p, hsa-miR-6729-5p, hsa-miR-4632-5p, hsa-miR-615-5p, hsa-miR-6724-5p, hsa-miR-4728-5p, hsa-miR-6732-5p, hsa-miR-6816-5p, hsa-miR-4695-5p, hsa-miR-6088, hsa-miR-7975, hsa-miR-3197, hsa-miR-6125, hsa-miR-4433-3p, hsa-miR-6727-5p, hsa-miR-4706, hsa-miR-7847-3p, hsa-miR-6805-3p, hsa-miR-6766-3p, hsa-miR-1913, hsa-miR-4649-5p, hsa-miR-602, hsa-miR-3663-3p, hsa-miR-6893-5p, hsa-miR-6861-5p, hsa-miR-4449, hsa-miR-6842-5p, hsa-miR-4454, hsa-miR-5195-3p, hsa-miR-663b, hsa-miR-6765-5p, hsa-miR-4513, hsa-miR-614, hsa-miR-6785-5p, hsa-miR-6777-5p, hsa-miR-940, hsa-miR-4741, hsa-miR-6870-5p, hsa-miR-6131, hsa-miR-150-3p, hsa-miR-4707-5p, hsa-miR-1915-3p, hsa-miR-3937, hsa-miR-937-5p, hsa-miR-4443, hsa-miR-1914-3p, hsa-miR-3620-5p, hsa-miR-1268b, hsa-miR-1227-5p, hsa-miR-6880-5p, hsa-miR-4417, hsa-miR-6802-5p, hsa-miR-6769a-5p, hsa-miR-663a, hsa-miR-6721-5p, hsa-miR-4532, hsa-miR-7977, hsa-miR-92b-5p, hsa-miR-371a-5p, hsa-miR-6126, hsa-miR-4734, hsa-miR-4665-3p, hsa-miR-423-5p, hsa-miR-1469, hsa-miR-4675, hsa-miR-1915-5p, hsa-miR-6716-5p, hsa-miR-718, hsa-miR-4281, hsa-miR-6820-5p, hsa-miR-6795-5p, hsa-miR-6779-5p, hsa-miR-7109-5p, hsa-miR-6798-5p, hsa-miR-4648, hsa-miR-8059, hsa-miR-6765-3p, hsa-miR-6132, hsa-miR-4492, hsa-miR-7107-5p, hsa-miR-3195, hsa-miR-3180, hsa-miR-296-3p, hsa-miR-564, hsa-miR-1268a, hsa-miR-6848-5p, hsa-miR-762, hsa-miR-2861, hsa-miR-1203, hsa-miR-1260b, hsa-miR-4476, hsa-miR-6885-5p, hsa-miR-6769b-5p, hsa-miR-23b-3p, hsa-miR-1343-5p, hsa-miR-3621, hsa-miR-4688, hsa-miR-4286, hsa-miR-4640-5p, hsa-miR-4739, hsa-miR-1260a, hsa-miR-4276, hsa-miR-7106, hsa-miR-128-2-5p, hsa-miR-125a-3p, hsa-miR-92a-2-5p and hsa-miR-486-3p genes, and the nucleotide sequences of SEQ ID NOs: 1 to 169 related thereto were found.

[0586] Among them, genes newly found as markers for examining the presence or absence of stomach cancer are polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 165.

[0587] A discriminant for determining the presence or absence of stomach cancer was further prepared by Fisher's discriminant analysis with the expression levels of these genes as indicators. Specifically, any newly found polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 169 in the training cohort was applied for Formula 2 to construct a discriminant. Calculated accuracy, sensitivity, and specificity are shown in Table 3. In this respect, a discriminant coefficient and a constant term are shown in Table 4. In this context, all of the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 169 were selected as markers capable of determining all of papillary adenocarcinoma, tubular adenocarcinoma (3 cases), low differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous carcinoma, which are main types of stomach cancer.

[0588] Next, accuracy, sensitivity, and specificity in the validation cohort were calculated using the discriminant thus prepared, and the discriminant performance of the selected polynucleotides was validated using independent samples (Table 3). For example, the expression level measurement value of the nucleotide sequence represented by SEQ ID NO: 1 was compared between the healthy subjects (100 persons) and the stomach cancer patients (34 persons) in the training cohort. As a result, the gene expression level measurement values were found to be significantly lower in the stomach cancer patient group than in the healthy subject group (see the left diagram of Figure 2). These results were also reproducible in the healthy subjects (50 persons) and the stomach cancer patients (16 persons) in the validation cohort (see the right diagram of Figure 2). Likewise, the results obtained about the other polynucleotides shown in SEQ ID NOs: 2 to 169 showed that the gene expression level measurement values were significantly lower (-) or higher (+) in the stomach cancer patient group than in the healthy subject group (Table 2). These results were able to be validated in the validation cohort. For example, as for this nucleotide sequence represented by SEQ ID NO: 1, the number of correctly or incorrectly identified samples in the detection of stomach cancer was calculated using the threshold (6.29) that was set in the training cohort and discriminated between the groups. As a result, 14 true positives, 49 true negatives, 1 false positive, and 2 false negatives were obtained. From these values, 95.5% accuracy, 87.5% sensitivity, and 98% specificity were obtained as the detection performance. In this way, the detection performance was calculated as to all of the polynucleotides shown in SEQ ID NOs: 1 to 169, and described in Table 3. The polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 169 shown in Table 3, exhibited sensitivity of 87.5%, 93.8%, 93.8%, 81.2%, 93.8%, 87.5%, 87.5%, 81.2%, 68.8%, 87.5%, 75.0%, 81.2%, 87.5%, 75.0%, 81.2%, 93.8%, 68.8%, 81.2%, 56.2%, 68.8%, 87.5%, 56.2%, 62.5%, 62.5%, 62.5%, 75.0%, 56.2%, 87.5%, 93.8%, 62.5%, 87.5%, 62.5%, 68.8%, 81.2%, 81.2%, 62.5%, 81.2%, 81.2%, 62.5%, 87.5%, 62.5%, 75.0%, 56.2%, 75.0%, 62.5%, 56.2%, 68.8%, 62.5%, 56.2%, 93.8%, 62.5%, 62.5%, 56.2%, 81.2%, 68.8%, 56.2%, 43.8%, 75.0%, 75.0%, 68.8%, 81.2%, 75.0%, 68.8%, 68.8%, 43.8%, 62.5%, 50.0%, 50.0%, 62.5%, 62.5%, 50.0%, 68.8%, 37.5%, 50.0%, 37.5%, 68.8%, 68.8%, 56.2%, 12.5%, 75.0%, 50.0%, 50.0%, 37.5%, 68.8%, 25.0%, 81.2%, 43.8%, 56.2%, 62.5%, 37.5%, 43.8%, 43.8%, 37.5%, 43.8%, 31.2%, 43.8%, 50.0%, 25%, 43.8%, 37.5%, 37.5%, 31.2%, 25.0%, 25.0%, 56.2%, 31.2%, 43.8%, 56.2%, 50.0%, 37.5%, 31.2%, 31.2%, 37.5%, 50.0%, 12.5%, 31.2%, 56.2%, 18.8%, 43.8%, 18.8%, 37.5%, 31.2%, 37.5%, 50.0%, 50.0%, 12.5%, 31.2%, 31.2%, 31.2%, 31.2%, 50.0%, 37.5%, 18.8%, 37.5%, 50.0%, 43.8%, 18.8%, 43.8%, 31.2%, 18.8%, 50.0%, 25.0%, 31.2%, 31.2%, 18.8%, 43.8%, 6.2%, 25.0%, 12.5%, 31.2%, 12.5%, 18.8%, 37.5%, 6.2%, 31.2%, 6.2%, 18.8%, 6.2%, 18.8%, 6.2%, 12.5%, 18.8%, 6.2%, 12.5%, 6.2%, 50.0%, 68.8%, 31.2%, and 25.0%, respectively, in the validation cohort. As seen from Comparative Example mentioned later, the existing markers CEA and CA19-9 had sensitivity of 12.5% (when the abnormal value of CEA was defined as 5 ng/ml or higher) and 12.5% (when the abnormal value of CA19-9 was defined as 37 U/ml or higher), respectively, in the validation cohort, demonstrating that all of the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 169 can discriminate, each alone, stomach cancer in the validation cohort with sensitivity beyond CEA and CA19-9.

[0589] For example, 4 polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 3, 5, 21, and 28 were able to correctly determine stomach cancer as to 9 stage IA stomach cancer samples contained in the validation cohort. Thus, these polynucleotides can detect even early stomach cancer and contribute to the early diagnosis of stomach cancer.

[Example 2]


<Method for evaluating stomach cancer discriminant performance by combination of multiple gene markers using samples in the validation cohort>



[0590] In this Example, a method for evaluating stomach cancer discriminant performance by a combination of the gene markers selected in Example 1 was studied. Specifically, Fisher's discriminant analysis was conducted as to 14,190 combinations of two expression level measurement values comprising at least one or more of the expression level measurement values of the newly found polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 165 among any of the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 169 selected in Example 1, to construct a discriminant for determining the presence or absence of stomach cancer. Next, accuracy, sensitivity, and specificity in the validation cohort were calculated using the discriminant thus prepared, and the discriminant performance of the selected polynucleotides was validated using the independent samples.

[0591] For example, the expression level measurement values of the nucleotide sequences represented by SEQ ID NO: 1 and SEQ ID NO: 2 were compared between the healthy subjects (100 persons) and the stomach cancer patients (34 persons) in the training cohort. As a result, a scatter diagram that significantly separated the expression level measurement values of the stomach cancer patient group from those of the healthy subject group was obtained (see the left diagram of Figure 3). These results were also reproducible in the healthy subjects (50 persons) and the stomach cancer patients (16 persons) in the validation cohort (see the right diagram of Figure 3). Likewise, a scatter diagram that significantly separated the gene expression level measurement values of the stomach cancer patient group from those of the healthy subject group was also obtained as to the other combinations of two expression level measurement values comprising at least one or more of the expression level measurement values of the newly found polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 165 among the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 169. These results were able to be validated in the validation cohort. For example, as for these nucleotide sequences represented by SEQ ID NO: 1 and SEQ ID NO: 2, the number of samples that were correctly or incorrectly identified in the detection of stomach cancer was calculated using the function (0 = 0.83x + y - 14.78) that was set in the training cohort and discriminated between the two groups. As a result, 15 true positives, 50 true negatives, 0 false positives, and 1 false negative were obtained. From these values, 98.5% accuracy, 93.8% sensitivity, and 100% specificity were obtained as the detection performance. In this way, the detection performance was calculated as to all of the combinations of two expression level measurement values comprising at least one or more of the expression level measurement values of any of the newly found polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 165 among the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 169. Among them, 168 combinations comprising the expression level measurement value of the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 1 and the detection performance thereof were described in Table 6 as an example. For example, a combination of the expression level measurement values of the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 and 14 exhibited sensitivity of 100% in the validation cohort. Also, all of combinations of two polynucleotides consisting of nucleotide sequences represented by SEQ ID NO: 1 and any of SEQ ID NOs: 2, 4, 14, 17, 22, 24, 27, 32, 39, 43, 46, 48, 53, 65, 66, 67, 78, 89, 91, 98, 99, 113, 116, 122, 129, 141, 144, 148, 150, 154, and 156 exhibited specificity of 100%. 14,159 combinations of the expression level measurement values of polynucleotides having sensitivity beyond the existing marker CEA or CA19-9 (both 12.5% in Table 5) were obtained in the validation cohort. All of the nucleotide sequences 1 to 165 described in Table 2 obtained in Example 1 were employed at least once in these combinations. These results demonstrated that the combined use of two of the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 165 can also discriminate stomach cancer with excellent performance beyond the existing marker. Thus, the combinations of two expression level measurement values of the polynucleotides consisting of the nucleotide sequences also produced excellent stomach cancer detection sensitivity.

[0592] Markers for the detection of stomach cancer with better sensitivity are obtained by further combining 3, 4, 5, 6, 7, 8, 9, 10 or more of the expression level measurement values of the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 169. For example, the newly found polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 165 among the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 169 selected in Example 1 were measured to obtain their expression levels between the healthy subject group and the stomach cancer group in the validation cohort. All of the polynucleotides were ranked in the descending order of their P values based on the Student's t-test which indicates statistical significance of difference between groups (i.e., one having the lowest P value was ranked in the first place), and stomach cancer detection sensitivity was evaluated using combinations of one or more polynucleotides to which the polynucleotides were added one by one from the top to the bottom according to the rank. In short, the order in which the polynucleotides were combined in this evaluation is in reverse in terms of SEQ ID NOs from SEQ ID NO: 165 to SEQ ID NOs: 164, 163, ... shown in Table 2. As a result, the sensitivity in the validation cohort was 6.2% for 1 polynucleotide (SEQ ID NO: 165), 62.5% for 2 polynucleotides (SEQ ID NOs: 165 and 164), 68.8% for 4 polynucleotides (SEQ ID NOs: 162 to 165), 75.0% for 8 polynucleotides (SEQ ID NOs: 158 to 165), 87.5% for 13 polynucleotides (SEQ ID NOs: 153 to 165), 93.8% for 15 polynucleotides (SEQ ID NOs: 151 to 165), 100% for 23 polynucleotides (SEQ ID NOs: 143 to 165), 100% for 50 polynucleotides (SEQ ID NOs: 116 to 165), 100% for 80 polynucleotides (SEQ ID NOs: 86 to 165), 100% for 100 polynucleotides (SEQ ID NOs: 66 to 165), 100% for 150 polynucleotides (SEQ ID NOs: 16 to 165), and 100% for 165 polynucleotides (SEQ ID NOs: 1 to 165).

[0593] These results demonstrated that a combination of multiple polynucleotides can produce higher stomach cancer discriminant performance than that of each polynucleotide alone or a combination of a fewer number of polynucleotides. In this context, the combinations of multiple polynucleotides are not limited to the combinations of the polynucleotides added in the order of statistically significant difference as described above, and any combination of multiple polynucleotides can be used in the detection of stomach cancer.

[0594] From these results, it can be concluded that all of the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 169 serve as excellent markers for the detection of stomach cancer.
[Table 2]
SEQ ID NO:Gene nameP value after Bonferroni correctionExpression level in stomach cancer patient relative to healthy subject
1 hsa-miR-4257 1. 77.E-35 -
2 hsa-miR-6726-5p 1.21.E-34 -
3 hsa-miR-1343-3p 2.35.E-27 -
4 hsa-miR-1247-3p 1.41.E-25 +
5 hsa-miR-6787-5p 9.96.E-25 -
6 hsa-miR-6875-5p 3.18.E-23 +
7 hsa-miR-1225-3p 4.17.E-23 +
8 hsa-miR-8063 1.39.E-22 -
9 hsa-miR-6781-5p 4.80.E-22 +
10 hsa-miR-4746-3p 7.08.E-22 +
11 hsa-miR-1908-5p 1.66.E-21 +
12 hsa-miR-6756-5p 2.78.E-21 -
13 hsa-miR-204-3p 3.60.E-21 -
14 hsa-miR-4651 3.74.E-21 -
15 hsa-miR-6757-5p 5.50.E-21 -
16 hsa-miR-6825-5p 7.04.E-20 +
17 hsa-miR-7108-5p 8.87.E-20 +
18 hsa-miR-4792 1.50.E-19 +
19 hsa-miR-7641 2.77.E-19 -
20 hsa-miR-3188 4.51.E-19 +
21 hsa-miR-3131 1.03.E-18 -
22 hsa-miR-6780b-5p 1.44.E-18 +
23 hsa-miR-8069 2.56.E-18 +
24 hsa-miR-6840-3p 3.01.E-18 -
25 hsa-miR-8072 4.25.E-18 +
26 hsa-miR-1233-5p 2.25.E-17 -
27 hsa-miR-6887-5p 4.74.E-17 -
28 hsa-miR-1231 5.08.E-17 +
29 hsa-miR-5572 1.08.E-16 +
30 hsa-miR-6738-5p 1.16.E-16 -
31 hsa-miR-6784-5p 1.68.E-16 +
32 hsa-miR-6791-5p 3.16.E-16 +
33 hsa-miR-6749-5p 3.69.E-16 -
34 hsa-miR-6741-5p 5.38.E-16 -
35 hsa-miR-128-1-5p 1.67.E-15 +
36 hsa-miR-4419b 2.16.E-15 -
37 hsa-miR-6746-5p 2.49.E-15 -
38 hsa-miR-3184-5p 2.56.E-15 +
39 hsa-miR-3679-5p 2.88.E-15 +
40 hsa-miR-7110-5p 3.95.E-15 +
41 hsa-miR-4516 4.43.E-15 -
42 hsa-miR-6717-5p 4.77.E-15 -
43 hsa-miR-6826-5p 4.94.E-15 -
44 hsa-miR-4433b-3p 5.34.E-15 +
45 hsa-miR-3679-3p 2.55.E-14 +
46 hsa-miR-3135b 3.35.E-14 -
47 hsa-miR-3622a-5p 4.36.E-14 -
48 hsa-miR-711 5.86.E-14 +
49 hsa-miR-4467 7.26.E-14 +
50 hsa-miR-6857-5p 2.73.E-13 +
51 hsa-miR-6515-3p 3.28.E-13 +
52 hsa-miR-1225-5p 4.67.E-13 +
53 hsa-miR-187-5p 5.39.E-13 -
54 hsa-miR-3185 6.80.E-13 +
55 hsa-miR-642b-3p 8.60.E-13 -
56 hsa-miR-1249 1.16.E-12 +
57 hsa-miR-744-5p 2.15.E-12 +
58 hsa-miR-4442 3.26.E-12 -
59 hsa-miR-1228-3p 4.54.E-12 +
60 hsa-miR-939-5p 7.77.E-12 +
61 hsa-miR-6845-5p 9.25.E-12 +
62 hsa-miR-887-3p 1.35.E-11 +
63 hsa-miR-7845-5p 1.81.E-11 +
64 hsa-miR-6729-5p 2.80.E-11 +
65 hsa-miR-4632-5p 6.45.E-11 +
66 hsa-miR-615-5p 7.56.E-11 -
67 hsa-miR-6724-5p 8.75.E-11 +
68 hsa-miR-4728-5p 1.05.E-10 -
69 hsa-miR-6732-5p 1.23.E-10 +
70 hsa-miR-6816-5p 1.35.E-10 +
71 hsa-miR-4695-5p 4.88.E-10 +
72 hsa-miR-6088 5.46.E-10 -
73 hsa-miR-7975 5.48.E-10 -
74 hsa-miR-3197 5.56.E-10 +
75 hsa-miR-6125 6.01.E-10 +
76 hsa-miR-4433-3p 6.04.E-10 +
77 hsa-miR-6727-5p 8.92.E-10 -
78 hsa-miR-4706 1.09.E-09 -
79 hsa-miR-7847-3p 1.25.E-09 -
80 hsa-miR-6805-3p 1.57.E-09 +
81 hsa-miR-6766-3p 1.95.E-09 +
82 hsa-miR-1913 2.12.E-09 +
83 hsa-miR-4649-5p 2.42.E-09 -
84 hsa-miR-602 2.50.E-09 +
85 hsa-miR-3663-3p 2.83.E-09 -
86 hsa-miR-6893-5p 3.40.E-09 -
87 hsa-miR-6861-5p 3.53.E-09 -
88 hsa-miR-4449 4.40.E-09 +
89 hsa-miR-6842-5p 4.48.E-09 +
90 hsa-miR-4454 4.77.E-09 -
91 hsa-miR-5195-3p 6.01.E-09 -
92 hsa-miR-663b 9.12.E-09 -
93 hsa-miR-6765-5p 2.06.E-08 +
94 hsa-miR-4513 2.61.E-08 -
95 hsa-miR-614 4.92.E-08 -
96 hsa-miR-6785-5p 5.85.E-08 -
97 hsa-miR-6777-5p 6.02.E-08 -
98 hsa-miR-940 8.08.E-08 +
99 hsa-miR-4741 9.53.E-08 +
100 hsa-miR-6870-5p 1.07.E-07 +
101 hsa-miR-6131 1.21.E-07 -
102 hsa-miR-150-3p 1.31.E-07 -
103 hsa-miR-4707-5p 1.70.E-07 +
104 hsa-miR-1915-3p 2.00.E-07 +
105 hsa-miR-3937 2.17.E-07 +
106 hsa-miR-937-5p 2.85.E-07 -
107 hsa-miR-4443 3.12.E-07 +
108 hsa-miR-1914-3p 3.23.E-07 -
109 hsa-miR-3620-5p 3.97.E-07 +
110 hsa-miR-1268b 5.51.E-07 +
111 hsa-miR-1227 -5p 8.69.E-07 +
112 hsa-miR-6880-5p 9.59.E-07 +
113 hsa-miR-4417 1.28.E-06 +
114 hsa-miR-6802-5p 1.30.E-06 -
115 hsa-miR-6769a-5p 1.32.E-06 -
116 hsa-miR-663a 1.42.E-06 +
117 hsa-miR-6721-5p 1.73.E-06 +
118 hsa-miR-4532 2.01.E-06 -
119 hsa-miR-7977 2.27.E-06 -
120 hsa-miR-92b-5p 2.37.E-06 +
121 hsa-miR-371a-5p 2.37.E-06 -
122 hsa-miR-6126 2.47.E-06 +
123 hsa-miR-4734 2.53.E-06 +
124 hsa-miR-4665-3p 2.71.E-06 +
125 hsa-miR-423-5p 4.04.E-06 -
126 hsa-miR-1469 8.08.E-06 +
127 hsa-miR-4675 8.36.E-06 -
128 hsa-miR-1915-5p 8.49.E-06 -
129 hsa-miR-6716-5p 9.56.E-06 +
130 hsa-miR-718 1.59.E-05 +
131 hsa-miR-4281 1.59.E-05 -
132 hsa-miR-6820-5p 1.88.E-05 -
133 hsa-miR-6795-5p 3.14.E-05 -
134 hsa-miR-6779-5p 3.55.E-05 -
135 hsa-miR-7109-5p 4.02.E-05 -
136 hsa-miR-6798-5p 4.28.E-05 +
137 hsa-miR-4648 6.38.E-05 +
138 hsa-miR-8059 7.15.E-05 -
139 hsa-miR-6765-3p 8.47.E-05 -
140 hsa-miR-6132 1.28.E-04 +
141 hsa-miR-4492 1.51.E-04 +
142 hsa-miR-7107-5p 1.64.E-04 -
143 hsa-miR-3195 1.73.E-04 +
144 hsa-miR-3180 2.82.E-04 +
145 hsa-miR-296-3p 2.89.E-04 -
146 hsa-miR-564 4.75.E-04 -
147 hsa-miR-1268a 5.55.E-04 +
148 hsa-miR-6848-5p 6.07.E-04 +
149 hsa-miR-762 8.99.E-04 +
150 hsa-miR-2861 1.57.E-03 -
151 hsa-miR-1203 1.91.E-03 +
152 hsa-miR-1260b 2.01.E-03 -
153 hsa-miR-4476 2.45.E-03 -
154 hsa-miR-6885-5p 2.83.E-03 -
155 hsa-miR-6769b-5p 2.84.E-03 -
156 hsa-miR-23b-3p 2.87.E-03 -
157 hsa-miR-1343-5p 3.95.E-03 +
158 hsa-miR-3621 4.31.E-03 -
159 hsa-miR-4688 4.77.E-03 -
160 hsa-miR-4286 4.90.E-03 -
161 hsa-miR-4640-5p 6.06.E-03 +
162 hsa-miR-4739 6.13.E-03 +
163 hsa-miR-1260a 7.24.E-03 -
164 hsa-miR-4276 8.00.E-03 +
165 hsa-miR-7106-5p 9.50.E-03 -
166 hsa-miR-128-2-5p 1.79.E-09 -
167 hsa-miR-125a-3p 1.81.E-09 -
168 hsa-miR-92a-2-5p 2.01.E-05 +
169 hsa-miR-486-3p 2.60.E-03 -
[Table 3]
 Training cohortValidation cohort
SEQ ID NO:Accuracy (%)Sensitivity (%)Specificity (%)Accuracy (%)Sensitivity (%)Specificity (%)
1 95.5 85.3 99.0 95.5 87.5 98.0
2 94.8 88.2 97.0 97.0 93.8 98.0
3 97.0 91.2 99.0 97.0 93.8 98.0
4 93.3 82.4 97.0 90.9 81.2 94.0
5 93.3 79.4 98.0 97.0 93.8 98.0
6 94.0 91.2 95.0 87.9 87.5 88.0
7 92.5 82.4 96.0 97.0 87.5 100.0
8 90.3 88.2 91.0 90.9 81.2 94.0
9 94.8 85.3 98.0 86.4 68.8 92.0
10 91.0 76.5 96.0 95.5 87.5 98.0
11 90.3 82.4 93.0 89.4 75.0 94.0
12 90.3 73.5 96.0 87.9 81.2 90.0
13 91.0 73.5 97.0 81.8 87.5 80.0
14 91.8 79.4 96.0 92.4 75.0 98.0
15 90.3 76.5 95.0 95.5 81.2 100.0
16 88.1 82.4 90.0 92.4 93.8 92.0
17 88.1 73.5 93.0 83.3 68.8 88.0
18 92.5 88.2 94.0 93.9 81.2 98.0
19 88.1 73.5 93.0 83.3 56.2 92.0
20 91.8 85.3 94.0 90.9 68.8 98.0
21 91.8 76.5 97.0 95.5 87.5 98.0
22 88.8 70.6 95.0 89.4 56.2 100.0
23 88.1 67.6 95.0 87.9 62.5 96.0
24 87.3 64.7 95.0 87.9 62.5 96.0
25 88.1 61.8 97.0 83.3 62.5 90.0
26 90.3 76.5 95.0 89.4 75.0 94.0
27 91.0 67.6 99.0 89.4 56.2 100.0
28 90.3 79.4 94.0 90.9 87.5 92.0
29 85.8 79.4 88.0 90.9 93.8 90.0
30 89.6 76.5 94.0 86.4 62.5 94.0
31 85.1 73.5 89.0 87.9 87.5 88.0
32 85.1 67.6 91.0 89.4 62.5 98.0
33 87.3 61.8 96.0 90.9 68.8 98.0
34 90.3 70.6 97.0 89.4 81.2 92.0
35 89.6 82.4 92.0 84.8 81.2 86.0
36 90.3 73.5 96.0 89.4 62.5 98.0
37 90.3 70.6 97.0 92.4 81.2 96.0
38 87.3 82.4 89.0 90.9 81.2 94.0
39 90.3 76.5 95.0 90.9 62.5 100.0
40 87.3 76.5 91.0 89.4 87.5 90.0
41 90.3 61.8 100.0 90.9 62.5 100.0
42 90.3 61.8 100.0 93.9 75.0 100.0
43 90.3 67.6 98.0 89.4 56.2 100.0
44 87.3 73.5 92.0 81.8 75.0 84.0
45 90.3 82.4 93.0 83.3 62.5 90.0
46 90.3 70.6 97.0 87.9 56.2 98.0
47 85.1 47.1 98.0 90.9 68.8 98.0
48 86.6 64.7 94.0 89.4 62.5 98.0
49 83.6 73.5 87.0 86.4 56.2 96.0
50 90.3 79.4 94.0 95.5 93.8 96.0
51 84.3 61.8 92.0 77.3 62.5 82.0
52 87.3 64.7 95.0 84.8 62.5 92.0
53 84.3 52.9 95.0 87.9 56.2 98.0
54 85.8 67.6 92.0 90.9 81.2 94.0
55 87.3 64.7 95.0 90.9 68.8 98.0
56 86.5 67.6 92.9 80.3 56.2 88.0
57 83.6 52.9 94.0 84.8 43.8 98.0
58 85.8 70.6 91.0 87.9 75.0 92.0
59 84.3 55.9 94.0 86.4 75.0 90.0
60 82.8 73.5 86.0 83.3 68.8 88.0
61 85.1 52.9 96.0 87.9 81.2 90.0
62 82.8 61.8 90.0 84.8 75.0 88.0
63 85.1 58.8 94.0 86.4 68.8 92.0
64 79.9 50.0 90.0 81.8 68.8 86.0
65 88.1 61.8 97.0 84.8 43.8 98.0
66 83.6 41.2 98.0 89.4 62.5 98.0
67 82.8 55.9 92.0 78.8 50.0 88.0
68 78.4 44.1 90.0 81.8 50.0 92.0
69 82.1 61.8 89.0 80.3 62.5 86.0
70 82.1 58.8 90.0 84.8 62.5 92.0
71 79.9 47.1 91.0 83.3 50.0 94.0
72 79.9 50.0 90.0 86.4 68.8 92.0
73 80.6 41.2 94.0 78.8 37.5 92.0
74 85.8 61.8 94.0 83.3 50.0 94.0
75 81.3 44.1 94.0 81.8 37.5 96.0
76 81.3 61.8 88.0 83.3 68.8 88.0
77 86.6 67.6 93.0 90.9 68.8 98.0
78 85.1 58.8 94.0 84.8 56.2 94.0
79 85.1 44.1 99.0 78.8 12.5 100.0
80 79.9 50.0 90.0 89.4 75.0 94.0
81 82.8 47.1 95.0 80.3 50.0 90.0
82 82.1 55.9 91.0 78.5 50.0 87.8
83 84.3 50.0 96.0 81.8 37.5 96.0
84 82.8 52.9 93.0 87.9 68.8 94.0
85 82.8 47.1 95.0 78.8 25.0 96.0
86 85.8 52.9 97.0 92.4 81.2 96.0
87 84.3 50.0 96.0 81.8 43.8 94.0
88 80.6 38.2 95.0 86.4 56.2 96.0
89 81.3 41.2 95.0 87.9 62.5 96.0
90 81.3 47.1 93.0 78.8 37.5 92.0
91 82.1 47.1 94.0 81.8 43.8 94.0
92 83.6 47.1 96.0 86.4 43.8 100.0
93 82.8 47.1 95.0 80.3 37.5 94.0
94 79.1 29.4 96.0 83.3 43.8 96.0
95 76.9 38.2 90.0 78.8 31.2 94.0
96 81.3 44.1 94.0 83.3 43.8 96.0
97 79.9 38.2 94.0 83.3 50.0 94.0
98 80.6 44.1 93.0 78.8 25.0 96.0
99 82.1 50.0 93.0 80.3 43.8 92.0
100 81.3 38.2 96.0 84.8 37.5 100.0
101 85.1 50.0 97.0 83.3 37.5 98.0
102 80.6 29.4 98.0 77.3 31.2 92.0
103 76.1 32.4 91.0 75.8 25.0 92.0
104 84.3 50.0 96.0 80.3 25.0 98.0
105 79.1 38.2 93.0 84.8 56.2 94.0
106 82.8 44.1 96.0 81.8 31.2 98.0
107 82.1 44.1 95.0 83.3 43.8 96.0
108 81.3 47.1 93.0 80.3 56.2 88.0
109 79.9 38.2 94.0 81.8 50.0 92.0
110 74.6 32.4 89.0 72.7 37.5 84.0
111 81.3 44.1 94.0 75.8 31.2 90.0
112 82.8 47.1 95.0 80.3 31.2 96.0
113 81.3 35.3 97.0 81.8 37.5 96.0
114 86.6 52.9 98.0 86.4 50.0 98.0
115 79.1 38.2 93.0 75.8 12.5 96.0
116 81.3 41.2 95.0 78.8 31.2 94.0
117 76.9 38.2 90.0 80.3 56.2 88.0
118 81.3 38.2 96.0 75.8 18.8 94.0
119 78.4 35.3 93.0 81.8 43.8 94.0
120 78.4 38.2 92.0 78.8 18.8 98.0
121 79.1 35.3 94.0 75.8 37.5 88.0
122 78.4 38.2 92.0 81.8 31.2 98.0
123 78.4 32.4 94.0 80.3 37.5 94.0
124 87.3 52.9 99.0 86.4 50.0 98.0
125 76.9 32.4 92.0 75.8 50.0 84.0
126 78.4 29.4 95.0 71.2 12.5 90.0
127 80.6 41.2 94.0 83.3 31.2 100.0
128 79.9 32.4 96.0 78.8 31.2 94.0
129 77.6 26.5 95.0 77.3 31.2 92.0
130 76.1 26.5 93.0 75.8 31.2 90.0
131 78.4 35.3 93.0 84.8 50.0 96.0
132 80.6 29.4 98.0 77.3 37.5 90.0
133 79.9 23.5 99.0 80.3 18.8 100.0
134 75.4 32.4 90.0 83.3 37.5 98.0
135 73.9 23.5 91.0 80.3 50.0 90.0
136 78.4 44.1 90.0 74.2 43.8 84.0
137 73.9 20.6 92.0 80.3 18.8 100.0
138 79.1 29.4 96.0 81.8 43.8 94.0
139 82.1 41.2 96.0 80.3 31.2 96.0
140 79.9 29.4 97.0 78.8 18.8 98.0
141 79.1 32.4 95.0 81.8 50.0 92.0
142 75.4 29.4 91.0 75.8 25.0 92.0
143 78.4 38.2 92.0 77.3 31.2 92.0
144 79.9 32.4 96.0 81.8 31.2 98.0
145 81.2 27.3 99.0 77.3 18.8 96.0
146 81.3 35.3 97.0 84.8 43.8 98.0
147 73.1 14.7 93.0 71.2 6.2 92.0
148 77.6 23.5 96.0 78.8 25.0 96.0
149 77.6 23.5 96.0 72.3 12.5 91.8
150 77.6 23.5 96.0 80.3 31.2 96.0
151 74.6 14.7 95.0 78.8 12.5 100.0
152 79.9 32.4 96.0 75.8 18.8 94.0
153 76.1 20.6 95.0 78.8 37.5 92.0
154 81.3 32.4 98.0 75.8 6.2 98.0
155 76.9 20.6 96.0 81.8 31.2 98.0
156 79.1 23.5 98.0 72.7 6.2 94.0
157 82.1 35.3 98.0 80.3 18.8 100.0
158 74.6 11.8 96.0 74.2 6.2 96.0
159 77.6 20.6 97.0 78.8 18.8 98.0
160 75.4 20.6 94.0 71.2 6.2 92.0
161 78.4 26.5 96.0 78.8 12.5 100.0
162 79.1 20.6 99.0 78.8 18.8 98.0
163 76.1 20.6 95.0 72.7 6.2 94.0
164 76.9 14.7 98.0 78.8 12.5 100.0
165 74.6 8.8 97.0 75.8 6.2 98.0
166 85.1 52.9 96.0 87.9 50.0 100.0
167 85.8 50.0 98.0 89.4 68.8 96.0
168 80.6 41.2 94.0 77.3 31.2 92.0
169 80.6 32.4 97.0 81.8 25.0 100.0
[Table 4]
SEQ ID NO:Discriminant coefficientConstant term
1 2.731 17.177
2 3.324 31.765
3 1.836 12.851
4 4.010 25.699
5 3.767 31.391
6 3.829 35.096
7 3.144 17.990
8 2.726 21.913
9 5.443 57.639
10 2.686 18.095
11 4.398 51.318
12 5.286 43.176
13 1.921 24.270
14 5.407 58.548
15 2.820 19.731
16 2.197 14.682
17 4.707 43.642
18 2.022 13.892
19 1.268 8.665
20 3.417 21.034
21 2.266 15.207
22 3.039 27.590
23 7.728 99.955
24 3.052 26.321
25 5.366 66.791
26 2.810 30.883
27 2.291 13.933
28 3.580 23.815
29 2.466 16.690
30 3.715 25.964
31 3.866 49.046
32 4.847 44.998
33 4.518 44.908
34 4.174 28.253
35 2.781 21.080
36 2.163 12.587
37 2.399 14.923
38 2.387 19.533
39 2.662 18.538
40 1.844 14.656
41 4.162 54.280
42 1.861 10.860
43 1.882 10.852
44 3.955 32.182
45 3.509 21.353
46 2.764 21.183
47 2.237 12.508
48 3.474 29.057
49 2.348 23.412
50 1.601 8.585
51 4.385 29.783
52 3.501 25.951
53 2.121 20.821
54 2.398 17.081
55 2.333 21.669
56 3.979 23.944
57 2.618 18.423
58 3.487 32.829
59 4.222 26.720
60 2.479 18.929
61 3.944 38.152
62 2.371 17.392
63 2.987 20.097
64 9.232 116.333
65 4.246 34.038
66 1.900 12.014
67 4.891 49.041
68 5.062 35.194
69 3.378 28.973
70 4.587 46.523
71 4.446 33.529
72 3.367 33.945
73 2.155 21.186
74 2.768 26.384
75 5.220 62.722
76 3.883 28.652
77 5.643 71.747
78 3.610 27.579
79 2.457 15.182
80 2.520 19.029
81 3.853 22.961
82 3.525 21.894
83 2.531 25.858
84 3.041 19.506
85 3.868 46.680
86 2.117 17.685
87 3.724 26.711
88 3.680 23.968
89 3.374 20.135
90 2.196 25.309
91 2.976 20.156
92 2.933 25.402
93 5.009 53.145
94 2.567 14.765
95 1.729 11.402
96 2.393 21.401
97 3.112 20.031
98 3.065 19.720
99 3.850 38.303
100 3.191 23.796
101 1.739 18.155
102 1.790 11.695
103 4.223 31.086
104 3.902 43.384
105 4.394 38.067
106 3.808 31.650
107 2.442 15.680
108 4.742 35.456
109 4.065 32.357
110 3.132 31.233
111 6.253 59.917
112 2.144 16.593
113 5.077 41.640
114 4.331 36.232
115 4.104 26.007
116 4.365 44.632
117 4.092 30.958
118 3.410 40.413
119 2.277 22.244
120 3.385 27.099
121 3.662 26.864
122 3.020 32.940
123 5.127 61.295
124 2.499 14.725
125 2.372 17.057
126 5.371 54.883
127 2.882 21.683
128 1.355 8.339
129 3.793 24.904
130 3.673 25.051
131 3.824 44.211
132 2.858 20.620
133 2.687 15.927
134 6.294 44.652
135 5.392 39.920
136 2.883 30.122
137 1.419 8.435
138 3.372 25.593
139 1.616 14.087
140 3.505 27.638
141 5.430 57.153
142 4.737 36.945
143 4.079 33.703
144 4.615 40.322
145 1.899 11.130
146 1.461 8.484
147 3.248 36.484
148 4.537 33.621
149 6.451 87.375
150 5.814 72.020
151 2.391 14.618
152 2.345 19.966
153 1.746 12.413
154 2.794 30.977
155 3.878 24.272
156 1.014 5.894
157 3.451 35.923
158 4.810 57.343
159 3.755 26.714
160 2.474 18.364
161 4.014 31.043
162 3.561 40.868
163 2.408 16.644
164 1.795 10.022
165 2.135 12.545
166 2.652 28.430
167 1.220 7.446
168 2.017 19.036
169 2.835 22.505
[Table 5-1]
Training cohort
Sample nameCancer stageCEACA19-9
SC03 IA 2.9(-) 77.4(+)
SC04 IA 2.9(-) 0.1(-)
SC05 IA 2.9(-) 21.8(-)
SC06 IA 1.7(-) 41.9(+)
SC07 IB 1.5(-) 25.1(-)
SC09 IA 2.3(-) 17.5(-)
SC10 IIB 1.2(-) 10.0(-)
SC12 IA 3.3(-) 8.5(-)
SC13 IA 3.4(-) 8.2(-)
SC15 IA 3.7(-) 6.3(-)
SC17 IIB 2.8(-) 4.3(-)
SC18 IB 6.9(+) 20.2(-)
SC19 IA 3.1(-) 5.0(-)
SC20 IIIC 3.3(-) 20.1(-)
SC23 IB 2.5(-) 0.1(-)
SC24 IA 3.1(-) 43.2(+)
SC25 IIIA 2.6(-) 16.4(-)
SC26 IA 0.9(-) 7.3(-)
SC27 IA 2.0(-) 9.2(-)
SC29 IIA 1.3(-) 35.6(-)
SC30 IA 2.8(-) 0.1(-)
SC31 IA 2.4(-) 14.0(-)
SC32 IA 4.0(-) 10.5(-)
SC34 IA 2.4(-) 17.0(-)
SC36 IIIC 1.5(-) 14.1(-)
SC38 IA 4.8(-) 47.6(+)
SC40 IIA 1.7(-) 29.4(-)
SC41 IA 0.3(-) 10.9(-)
SC42 IIIA 2.2(-) 12.2(-)
SC45 IIIC 0.8(-) 6.5(-)
SC47 IB 1.3(-) 26.3(-)
SC48 IIIA 1.9(-) 6.3(-)
SC49 IA 2.9(-) 41.1(+)
SC50 IB 1.4(-) 11.4(-)
[Table 5-2]
Validation cohort
Sample nameCancer stageCEACA19/9
SC01 IA 3.7(-) 0.1(-)
SC02 IA 4.9(-) 65.2(+)
SC08 IA 1.1(-) 9.9(-)
SC11 IA 1.8(-) 9.4(-)
SC14 IB 2.0(-) 26.1(-)
SC16 IA 3.1(-) 9.5(-)
SC21 IIA 0.7(-) 9.1(-)
SC22 IA 1.4(-) 6.0(-)
SC28 IA 3.3(-) 6.6(-)
SC33 IIIA 5.6(+) 14.7(-)
SC35 IA 3.7(-) 7.8(-)
SC37 IIB 4.2(-) 0.1 (-)
SC39 IIIC 17.5(+) 7.0(-)
SC43 IIA 4.6(-) 10.1(-)
SC44 IA 1.8(-) 5.8(-)
SC46 IB 2.7(-) 37.1(+)
For CEA, 5 ng/mL or lower was indicated as "-", and for A19-9, 37 U/mL or lower was indicated as "-", while values exceeding these were indicated as "+".
[Table 6]
 Training cohortValidation cohort
SEQ ID NO:Accuracy (%)Sensitivity (%)Specificity (%)Accuracy (%)Sensitivity (%)Specificity (%)
1_2 100.0 100.0 100.0 98.5 93.8 100.0
1_3 97.8 94.1 99.0 95.5 87.5 98.0
1_4 98.5 94.1 100.0 98.5 93.8 100.0
1_5 96.3 88.2 99.0 95.5 87.5 98.0
1_6 97.0 91.2 99.0 93.9 87.5 96.0
1_7 96.3 91.2 98.0 95.5 87.5 98.0
1_8 95.5 88.2 98.0 95.5 87.5 98.0
1_9 97.0 91.2 99.0 95.5 87.5 98.0
1_10 97.0 91.2 99.0 95.5 87.5 98.0
1_11 96.3 88.2 99.0 95.5 87.5 98.0
1_12 96.3 88.2 99.0 93.9 87.5 96.0
1_13 100.0 100.0 100.0 93.9 93.8 94.0
1_14 97.8 94.1 99.0 100.0 100.0 100.0
1_15 95.5 85.3 99.0 95.5 87.5 98.0
1_16 96.3 88.2 99.0 95.5 87.5 98.0
1_17 96.3 91.2 98.0 95.5 81.2 100.0
1_18 96.3 88.2 99.0 95.5 87.5 98.0
1_19 100.0 100.0 100.0 95.5 87.5 98.0
1_20 96.3 88.2 99.0 95.5 87.5 98.0
1_21 95.5 85.3 99.0 95.5 87.5 98.0
1_22 97.8 91.2 100.0 95.5 81.2 100.0
1_23 99.3 97.1 100.0 95.5 87.5 98.0
1_24 96.3 88.2 99.0 97.0 87.5 100.0
1_25 99.3 97.1 100.0 95.5 87.5 98.0
1_26 96.3 88.2 99.0 93.9 87.5 96.0
1_27 96.3 88.2 99.0 97.0 87.5 100.0
1_28 96.3 88.2 99.0 97.0 93.8 98.0
1_29 95.5 88.2 98.0 95.5 87.5 98.0
1_30 95.5 88.2 98.0 95.5 87.5 98.0
1_31 96.3 88.2 99.0 93.9 87.5 96.0
1_32 96.3 88.2 99.0 97.0 87.5 100.0
1_33 96.3 88.2 99.0 95.5 87.5 98.0
1_34 96.3 88.2 99.0 95.5 87.5 98.0
1_35 96.3 88.2 99.0 95.5 87.5 98.0
1_36 96.3 88.2 99.0 95.5 87.5 98.0
1_37 96.3 88.2 99.0 95.5 87.5 98.0
1_38 96.3 88.2 99.0 95.5 87.5 98.0
1_39 96.3 88.2 99.0 97.0 87.5 100.0
1_40 95.5 88.2 98.0 95.5 87.5 98.0
1_41 95.5 85.3 99.0 95.5 87.5 98.0
1_42 95.5 85.3 99.0 95.5 87.5 98.0
1_43 95.5 85.3 99.0 97.0 87.5 100.0
1_44 95.5 88.2 98.0 93.9 87.5 96.0
1_45 97.8 94.1 99.0 95.5 87.5 98.0
1_46 97.0 91.2 99.0 97.0 87.5 100.0
1_47 97.0 94.1 98.0 97.0 93.8 98.0
1_48 96.3 88.2 99.0 97.0 87.5 100.0
1_49 97.8 91.2 100.0 93.9 87.5 96.0
1_50 95.5 85.3 99.0 95.5 87.5 98.0
1_51 98.5 97.1 99.0 95.5 87.5 98.0
1_52 95.5 85.3 99.0 95.5 87.5 98.0
1_53 95.5 85.3 99.0 97.0 87.5 100.0
1_54 95.5 85.3 99.0 95.5 87.5 98.0
1_55 96.3 88.2 99.0 95.5 87.5 98.0
1_56 97.7 94.1 99.0 95.5 87.5 98.0
1_57 97.8 91.2 100.0 97.0 93.8 98.0
1_58 95.5 88.2 98.0 93.9 87.5 96.0
1_59 97.0 94.1 98.0 93.9 87.5 96.0
1_60 94.8 85.3 98.0 95.5 87.5 98.0
1_61 95.5 85.3 99.0 97.0 93.8 98.0
1_62 96.3 88.2 99.0 95.5 87.5 98.0
1_63 96.3 88.2 99.0 95.5 87.5 98.0
1_64 96.3 88.2 99.0 95.5 87.5 98.0
1_65 96.3 88.2 99.0 97.0 87.5 100.0
1_66 97.0 91.2 99.0 97.0 87.5 100.0
1_67 95.5 88.2 98.0 97.0 87.5 100.0
1_68 95.5 85.3 99.0 95.5 87.5 98.0
1_69 95.5 88.2 98.0 95.5 87.5 98.0
1_70 96.3 88.2 99.0 95.5 87.5 98.0
1_71 96.3 88.2 99.0 95.5 87.5 98.0
1_72 95.5 85.3 99.0 95.5 87.5 98.0
1_73 95.5 85.3 99.0 95.5 87.5 98.0
1_74 95.5 85.3 99.0 95.5 87.5 98.0
1_75 98.5 94.1 100.0 95.5 87.5 98.0
1_76 95.5 85.3 99.0 93.9 87.5 96.0
1_77 95.5 85.3 99.0 95.5 87.5 98.0
1_78 96.3 88.2 99.0 98.5 93.8 100.0
1_79 97.0 91.2 99.0 95.5 87.5 98.0
1_80 95.5 88.2 98.0 95.5 87.5 98.0
1_81 97.0 91.2 99.0 95.5 87.5 98.0
1_82 95.5 85.3 99.0 95.4 87.5 98.0
1_83 96.3 88.2 99.0 95.5 87.5 98.0
1_84 94.8 82.4 99.0 95.5 87.5 98.0
1_85 96.3 88.2 99.0 95.5 87.5 98.0
1_86 99.3 97.1 100.0 95.5 93.8 96.0
1_87 95.5 85.3 99.0 95.5 87.5 98.0
1_88 96.3 88.2 99.0 95.5 87.5 98.0
1_89 96.3 88.2 99.0 97.0 87.5 100.0
1_90 95.5 85.3 99.0 95.5 87.5 98.0
1_91 96.3 91.2 98.0 97.0 87.5 100.0
1_92 96.3 88.2 99.0 95.5 87.5 98.0
1_93 96.3 88.2 99.0 95.5 87.5 98.0
1_94 96.3 88.2 99.0 95.5 87.5 98.0
1_95 96.3 88.2 99.0 95.5 87.5 98.0
1_96 95.5 85.3 99.0 95.5 87.5 98.0
1_97 97.0 91.2 99.0 95.5 87.5 98.0
1_98 95.5 91.2 97.0 97.0 87.5 100.0
1_99 95.5 85.3 99.0 97.0 87.5 100.0
1_100 96.3 88.2 99.0 95.5 87.5 98.0
1_101 96.3 88.2 99.0 95.5 87.5 98.0
1_102 99.3 97.1 100.0 97.0 93.8 98.0
1_103 95.5 85.3 99.0 95.5 87.5 98.0
1_104 95.5 85.3 99.0 93.9 87.5 96.0
1_105 95.5 85.3 99.0 95.5 87.5 98.0
1_106 96.3 88.2 99.0 95.5 87.5 98.0
1_107 96.3 88.2 99.0 95.5 87.5 98.0
1_108 97.0 91.2 99.0 93.9 87.5 96.0
1_109 95.5 85.3 99.0 95.5 87.5 98.0
1_110 96.3 88.2 99.0 95.5 87.5 98.0
1_111 96.3 88.2 99.0 95.5 87.5 98.0
1_112 95.5 85.3 99.0 95.5 87.5 98.0
1_113 97.0 91.2 99.0 98.5 93.8 100.0
1_114 95.5 85.3 99.0 95.5 87.5 98.0
1_115 95.5 85.3 99.0 95.5 87.5 98.0
1_116 96.3 91.2 98.0 98.5 93.8 100.0
1_117 96.3 88.2 99.0 95.5 87.5 98.0
1_118 96.3 88.2 99.0 95.5 87.5 98.0
1_119 95.5 85.3 99.0 95.5 87.5 98.0
1_120 97.0 91.2 99.0 95.5 87.5 98.0
1_121 96.3 88.2 99.0 95.5 87.5 98.0
1_122 96.3 88.2 99.0 97.0 87.5 100.0
1_123 97.8 91.2 100.0 97.0 93.8 98.0
1_124 95.5 85.3 99.0 95.5 87.5 98.0
1_125 98.5 94.1 100.0 97.0 93.8 98.0
1_126 97.0 91.2 99.0 97.0 93.8 98.0
1_127 96.3 88.2 99.0 95.5 87.5 98.0
1_128 96.3 88.2 99.0 95.5 87.5 98.0
1_129 97.0 91.2 99.0 97.0 87.5 100.0
1_130 96.3 88.2 99.0 95.5 87.5 98.0
1_131 96.3 88.2 99.0 95.5 87.5 98.0
1_132 97.0 91.2 99.0 95.5 87.5 98.0
1_133 96.3 88.2 99.0 95.5 87.5 98.0
1_134 96.3 88.2 99.0 95.5 87.5 98.0
1_135 96.3 88.2 99.0 97.0 93.8 98.0
1_136 95.5 85.3 99.0 95.5 87.5 98.0
1_137 95.5 85.3 99.0 97.0 93.8 98.0
1_138 96.3 88.2 99.0 95.5 87.5 98.0
1_139 95.5 85.3 99.0 95.5 87.5 98.0
1_140 97.0 91.2 99.0 95.5 87.5 98.0
1_141 95.5 85.3 99.0 98.5 93.8 100.0
1_142 97.8 91.2 100.0 93.9 87.5 96.0
1_143 95.5 85.3 99.0 95.5 87.5 98.0
1_144 96.3 88.2 99.0 97.0 87.5 100.0
1_145 96.2 87.9 99.0 95.5 87.5 98.0
1_146 99.3 97.1 100.0 97.0 93.8 98.0
1_147 96.3 88.2 99.0 95.5 87.5 98.0
1_148 96.3 88.2 99.0 98.5 93.8 100.0
1_149 95.5 85.3 99.0 95.4 87.5 98.0
1_150 97.0 91.2 99.0 97.0 87.5 100.0
1_151 95.5 88.2 98.0 95.5 87.5 98.0
1_152 95.5 85.3 99.0 95.5 87.5 98.0
1_153 99.3 97.1 100.0 97.0 93.8 98.0
1_154 96.3 88.2 99.0 97.0 87.5 100.0
1_155 96.3 88.2 99.0 95.5 87.5 98.0
1_156 96.3 88.2 99.0 97.0 87.5 100.0
1_157 96.3 88.2 99.0 97.0 93.8 98.0
1_158 95.5 85.3 99.0 95.5 87.5 98.0
1_159 95.5 85.3 99.0 95.5 87.5 98.0
1_160 95.5 85.3 99.0 95.5 87.5 98.0
1_161 95.5 85.3 99.0 95.5 87.5 98.0
1_162 96.3 88.2 99.0 95.5 87.5 98.0
1_163 95.5 85.3 99.0 95.5 87.5 98.0
1_164 96.3 88.2 99.0 95.5 87.5 98.0
1_165 97.8 94.1 99.0 95.5 87.5 98.0
1_166 96.3 88.2 99.0 95.5 87.5 98.0
1_167 98.5 97.1 99.0 97.0 93.8 98.0
1_168 97.0 91.2 99.0 95.5 87.5 98.0
1_169 96.3 88.2 99.0 95.5 87.5 98.0

[Example 3]


<Selection of gene markers using all samples and method for evaluating stomach cancer discriminant performance of acquired gene markers>



[0595] In this Example, the samples of the training cohort and the validation cohort used in Examples 1 and 2 described above were integrated, and selection of a gene marker and evaluation of its stomach cancer discriminant performance were conducted using all of the samples.

[0596] Specifically, the expression levels in the sera of the 50 stomach cancer patients and the 150 healthy subject miRNA s obtained in the preceding Reference Examples were normalized by quantile normalization. In order to acquire diagnosis markers with higher reliability, only genes having a gene expression level of 26 or higher in 50% or more of the samples in either of the stomach cancer patient group or the healthy subject group were selected in the gene marker selection. In order to further acquire statistical significance for discriminating a stomach cancer patient group from a healthy subject group, the P value obtained by two-tailed t-test assuming equal variance as to each gene expression level was corrected by the Bonferroni method, and genes that satisfied p < 0.01 were selected as gene markers for use in explanatory variables of a discriminant and described in Table 7. In this way, hsa-miR-3196, hsa-miR-211-3p, hsa-miR-4271, hsa-miR-6851-5p, hsa-miR-149-3p, hsa-miR-4667-5p, hsa-miR-135a-3p, hsa-miR-4486, hsa-miR-4697-5p, hsa-miR-4725-3p, hsa-miR-6510-5p, hsa-miR-5001-5p, hsa-miR-4673, hsa-miR-4466, hsa-miR-23a-3p, hsa-miR-3656, hsa-miR-6782-5p, hsa-miR-4689, hsa-miR-451a, hsa-miR-4446-3p, hsa-miR-3180-3p, hsa-miR-642a-3p, hsa-miR-6889-5p, hsa-miR-3178, hsa-miR-4665-5p, hsa-miR-6722-3p, hsa-miR-30c-1-3p, hsa-miR-4507, hsa-miR-3141 and hsa-miR-1199-5p genes, and the nucleotide sequences of SEQ ID NOs: 170 to 199 related thereto were found in addition to the genes described in Table 2. As with the nucleotide sequences shown in SEQ ID NOs: 1 to 169, the results obtained about the polynucleotides shown in SEQ ID NOs: 170 to 199 also showed that the measurement values were significantly lower (-) or higher (+) in the stomach cancer patient group than in the healthy subject group (Table 7). These results were able to be validated in the validation cohort. Thus, the presence or absence of stomach cancer in the newly obtained samples can be determined by the methods described in Examples 1 and 2 by using, alone or in combination, the gene expression level measurement values described in Table 7.
[Table 7]
SEQ ID NO:Gene nameP value after Bonferroni correctionExpression level in stomach cancer patient relative to healthy subject
1 hsa-miR-4257 1.17.E-53 -
2 hsa-miR-6726-5p 1.13.E-52 -
3 hsa-miR-1343-3p 1.41.E-44 -
4 hsa-miR-1247-3p 5.94.E-35 +
5 hsa-miR-6787-5p 2.22.E-39 -
6 hsa-miR-6875-5p 1.92.E-30 +
7 hsa-miR-1225-3p 6.99.E-36 +
8 hsa-miR-8063 7.15.E-31 -
9 hsa-miR-6781-5p 4.27.E-31 +
10 hsa-miR-4746-3p 1.93.E-35 +
11 hsa-miR-1908-5p 1.34.E-32 +
12 hsa-miR-6756-5p 2.25.E-28 -
13 hsa-miR-204-3p 5.11.E-30 -
14 hsa-miR-4651 2.11.E-33 -
15 hsa-miR-6757-5p 2.11.E-34 -
16 hsa-miR-6825-5p 1.20.E-31 +
17 hsa-miR-7108-5p 3.88.E-25 +
18 hsa-miR-4792 5.31.E-29 +
19 hsa-miR-7641 1.72.E-27 -
20 hsa-miR-3188 3.58.E-30 +
21 hsa-miR-3131 3.98.E-33 -
22 hsa-miR-6780b-5p 4.88.E-28 +
23 hsa-miR-8069 7.94.E-21 +
24 hsa-miR-6840-3p 4.43.E-23 -
25 hsa-miR-8072 1.55.E-23 +
26 hsa-miR-1233-5p 3.51.E-26 -
27 hsa-miR-6887-5p 1.34.E-24 -
28 hsa-miR-1231 9.31.E-26 +
29 hsa-miR-5572 3.97.E-25 +
30 hsa-miR-6738-5p 2.02.E-21 -
31 hsa-miR-6784-5p 1.03.E-23 +
32 hsa-miR-6791-5p 2.63.E-22 +
33 hsa-miR-6749-5p 6.36.E-23 -
34 hsa-miR-6741-5p 6.07.E-23 -
35 hsa-miR-128-1-5p 3.13.E-20 +
36 hsa-miR-4419b 9.02.E-24 -
37 hsa-miR-6746-5p 1.60.E-25 -
38 hsa-miR-3184-5p 1.38.E-23 +
39 hsa-miR-3679-5p 6.33.E-26 +
40 hsa-miR-7110-5p 3.06.E-24 +
41 hsa-miR-4516 1.26.E-23 -
42 hsa-miR-6717-5p 6.77.E-26 -
43 hsa-miR-6826-5p 8.66.E-25 -
44 hsa-miR-4433b-3p 5.71.E-19 +
45 hsa-miR-3679-3p 2.22.E-19 +
46 hsa-miR-3135b 7.59.E-15 -
47 hsa-miR-3622a-5p 4.66.E-24 -
48 hsa-miR-711 9.88.E-22 +
49 hsa-miR-4467 3.85.E-21 +
50 hsa-miR-6857-5p 1.03.E-19 +
51 hsa-miR-6515-3p 5.53.E-16 +
52 hsa-miR-1225-5p 2.33.E-19 +
53 hsa-miR-187-5p 1.31.E-20 -
54 hsa-miR-3185 1.30.E-19 +
55 hsa-miR-642b-3p 2.56.E-18 -
56 hsa-miR-1249 5.41.E-19 +
57 hsa-miR-744-5p 9.41.E-20 +
58 hsa-miR-4442 1.75.E-17 -
59 hsa-miR-1228-3p 1.10.E-19 +
60 hsa-miR-939-5p 1.54.E-16 +
61 hsa-miR-6845-5p 5.15.E-20 +
62 hsa-miR-887-3p 2.86.E-15 +
63 hsa-miR-7845-5p 3.21.E-16 +
64 hsa-miR-6729-5p 6.04.E-16 +
65 hsa-miR-4632-5p 7.17.E-16 +
66 hsa-miR-615-5p 3.13.E-17 -
67 hsa-miR-6724-5p 6.37.E-15 +
68 hsa-miR-4728-5p 1.26.E-16 -
69 hsa-miR-6732-5p 5.05.E-14 +
70 hsa-miR-6816-5p 8.52.E-17 +
71 hsa-miR-4695-5p 2.40.E-14 +
72 hsa-miR-6088 7.13.E-16 -
73 hsa-miR-7975 1.51.E-14 -
74 hsa-miR-3197 5.56.E-16 +
75 hsa-miR-6125 2.29.E-15 +
76 hsa-miR-4433-3p 1.66.E-13 +
77 hsa-miR-6727-5p 1.77.E-15 -
78 hsa-miR-4706 2.89.E-15 -
79 hsa-miR-7847-3p 1.35.E-14 -
80 hsa-miR-6805-3p 5.87.E-17 +
81 hsa-miR-6766-3p 1.02.E-14 +
82 hsa-miR-1913 6.53.E-14 +
83 hsa-miR-4649-5p 1.20.E-13 -
84 hsa-miR-602 3.43.E-17 +
85 hsa-miR-3663-3p 2.10.E-13 -
86 hsa-miR-6893-5p 3.43.E-17 -
87 hsa-miR-6861-5p 4.41.E-14 -
88 hsa-miR-4449 2.00.E-16 +
89 hsa-miR-6842-5p 1.49.E-15 +
90 hsa-miR-4454 1.57.E-13 -
91 hsa-miR-5195-3p 6.87.E-14 -
92 hsa-miR-663b 1.51.E-12 -
93 hsa-miR-6765-5p 5.17.E-11 +
94 hsa-miR-4513 3.77.E-14 -
95 hsa-miR-614 1.11.E-11 -
96 hsa-miR-6785-5p 6.54.E-12 -
97 hsa-miR-6777-5p 2.92.E-14 -
98 hsa-miR-940 1.38.E-13 +
99 hsa-miR-4741 2.04.E-12 +
100 hsa-miR-6870-5p 4.12.E-14 +
101 hsa-miR-6131 1.02.E-12 -
102 hsa-miR-150-3p 1.47.E-10 -
103 hsa-miR-4707-5p 8.76.E-12 +
104 hsa-miR-1915-3p 4.55.E-13 +
105 hsa-miR-3937 6.01.E-12 +
106 hsa-miR-937-5p 3.22.E-11 -
107 hsa-miR-4443 3.16.E-10 +
108 hsa-miR-1914-3p 7.61.E-11 -
109 hsa-miR-3620-5p 7.63.E-11 +
110 hsa-miR-1268b 2.01.E-09 +
111 hsa-miR-1227-5p 3.14.E-10 +
112 hsa-miR-6880-5p 3.80.E-09 +
113 hsa-miR-4417 7.19.E-10 +
114 hsa-miR-6802-5p 4.37.E-11 -
115 hsa-miR-6769a-5p 3.34.E-09 -
116 hsa-miR-663a 7.98.E-11 +
117 hsa-miR-6721-5p 1.38.E-09 +
118 hsa-miR-4532 9.58.E-08 -
119 hsa-miR-7977 9.99.E-11 -
120 hsa-miR-92b-5p 1.77.E-08 +
121 hsa-miR-371a-5p 8.63.E-09 -
122 hsa-miR-6126 1.93.E-10 +
123 hsa-miR-4734 3.27.E-09 +
124 hsa-miR-4665-3p 6.99.E-14 +
125 hsa-miR-423-5p 1.58.E-08 -
126 hsa-miR-1469 8.71.E-07 +
127 hsa-miR-4675 2.67.E-10 -
128 hsa-miR-1915-5p 1.06.E-08 -
129 hsa-miR-6716-5p 7.56.E-09 +
130 hsa-miR-718 1.99.E-09 +
131 hsa-miR-4281 9.46.E-11 -
132 hsa-miR-6820-5p 1.42.E-08 -
133 hsa-miR-6795-5p 4.38.E-10 -
134 hsa-miR-6779-5p 2.99.E-08 -
135 hsa-miR-7109-5p 7.06.E-08 -
136 hsa-miR-6798-5p 7.93.E-07 +
137 hsa-miR-4648 2.21.E-09 +
138 hsa-miR-8059 1.44.E-08 -
139 hsa-miR-6765-3p 6.59.E-08 -
140 hsa-miR-6132 3.82.E-06 +
141 hsa-miR-4492 1.34.E-08 +
142 hsa-miR-7107-5p 1.84.E-06 -
143 hsa-miR-3195 6.91.E-08 +
144 hsa-miR-3180 1.11.E-07 +
145 hsa-miR-296-3p 2.56.E-06 -
146 hsa-miR-564 1.32.E-07 -
147 hsa-miR-1268a 1.25.E-04 +
148 hsa-miR-6848-5p 2.82.E-06 +
149 hsa-miR-762 5.66.E-04 +
150 hsa-miR-2861 1.45.E-06 -
151 hsa-miR-1203 7.90.E-07 +
152 hsa-miR-1260b 2.26.E-04 -
153 hsa-miR-4476 5.95.E-06 -
154 hsa-miR-6885-5p 5.73.E-05 -
155 hsa-miR-6769b-5p 1.91.E-07 -
156 hsa-miR-23b-3p 1.38.E-05 -
157 hsa-miR-1343-5p 7.73.E-06 +
158 hsa-miR-3621 3.64.E-05 -
159 hsa-miR-4688 1.47.E-05 -
160 hsa-miR-4286 3.79.E-03 -
161 hsa-miR-4640-5p 1.79.E-05 +
162 hsa-miR-4739 2.45.E-05 +
163 hsa-miR-1260a 7.35.E-04 -
164 hsa-miR-4276 3.45.E-07 +
165 hsa-miR-7106-5p 4.60.E-04 -
166 hsa-miR-128-2-5p 1.05.E-13 -
167 hsa-miR-125a-3p 2.30.E-15 -
168 hsa-miR-92a-2-5p 5.42.E-09 +
169 hsa-miR-486-3p 2.00.E-05 -
170 hsa-miR-3196 2.06.E-06 +
171 hsa-miR-211-3p 2.03.E-05 -
172 hsa-miR-4271 2.31.E-05 -
173 hsa-miR-6851-5p 2.68.E-05 +
174 hsa-miR-149-3p 2.75.E-05 -
175 hsa-miR-4667-5p 4.05.E-05 +
176 hsa-miR-135a-3p 4.28.E-05 +
177 hsa-miR-4486 6.68.E-05 +
178 hsa-miR-4697-5p 7.18.E-05 -
179 hsa-miR-4725-3p 8.16.E-05 +
180 hsa-miR-6510-5p 8.18.E-05 +
181 hsa-miR-5001-5p 1.92.E-04 -
182 hsa-miR-4673 2.32.E-04 +
183 hsa-miR-4466 3.06.E-04 -
184 hsa-miR-23a-3p 5.28.E-04 -
185 hsa-miR-3656 5.41.E-04 +
186 hsa-miR-6782-5p 7.05.E-04 +
187 hsa-miR-4689 1.01.E-03 -
188 hsa-miR-451a 1.22.E-03 -
189 hsa-miR-4446-3p 1.51.E-03 -
190 hsa-miR-3180-3p 1.64.E-03 +
191 hsa-miR-642a-3p 1.80.E-03 -
192 hsa-miR-6889-5p 1.91.E-03 +
193 hsa-miR-3178 2.08.E-03 +
194 hsa-miR-4665-5p 2.84.E-03 -
195 hsa-miR-6722-3p 3.22.E-03 +
196 hsa-miR-30c-1-3p 4.13.E-03 +
197 hsa-miR-4507 6.12.E-03 +
198 hsa-miR-3141 6.13.E-03 +
199 hsa-miR-1199-5p 7.28.E-03 -

[Example 4]


<Method for evaluating stomach cancer-specific discriminant performance by combination of multiple gene markers using samples of validation cohort>



[0597] In this Example, gene markers for diagnosis were selected by comparing gene expression levels of miRNAs in sera of stomach cancer patients with that of a control group consisting of healthy subjects, pancreatic cancer patients, bile duct cancer patients, colorectal cancer patients, liver cancer patients, and benign pancreaticobiliary disease patients in the same way as the method described in Example 1 using the gene markers selected in Example 1 with respect to the training cohort as the sample group described in Reference Example 2. The polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 635 to 642 thus selected were further combined therewith to study a method for evaluating stomach cancer-specific discriminant performance.

[0598] Specifically, first, the miRNA expression levels in the training cohort and the validation cohort obtained in Reference Example 2 mentioned above were combined and normalized by quantile normalization. Next, Fisher's discriminant analysis was conducted as to combinations of 1 to 6 expression level measurement values comprising at least one or more of the expression level measurement values of the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 165 and 635 to 642, to construct a discriminant for determining the presence or absence of stomach cancer. Next, accuracy, sensitivity, and specificity in the validation cohort were calculated using the discriminant thus prepared, with the stomach cancer patient group as a positive sample group and, on the other hand, the healthy subject group, the pancreatic cancer patient group, the bile duct cancer patient group, the colorectal cancer patient group, the liver cancer patient group, and the benign pancreaticobiliary disease patient group as a negative sample groups. The discriminant performance of the selected polynucleotides was validated using the independent samples.

[0599] Most of polynucleotides consisting of the nucleotide sequences represented by any of these SEQ ID NOs (SEQ ID NOs: 1 to 165 and 635 to 642 corresponding to the miRNA markers of Table 1) or complementary sequences thereof mentioned above were able to provide relatively high accuracy, sensitivity, and specificity in the determination of the presence or absence of stomach cancer, and furthermore, were able to specifically discriminate stomach cancer from the other cancers. For example, among the combinations of multiple polynucleotides selected from the group consisting of polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 9, 13, 21, 27, 34, 36, 66, 75, 95, 98, 108, 130, 135, 143, 155, 183, 185, 187, 191, 193, 194, 635, 636, 637, 638, 639, 640, 641 and 642 or complementary sequences thereof (the cancer type-specific polynucleotide group 1) as polynucleotides capable of specifically binding to target markers, combinations comprising at least one or more polynucleotides selected from the group consisting of polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 21, 34, 36, 98, and 155 or complementary sequences thereof (the cancer type-specific polynucleotide group 2) included in the cancer type-specific polynucleotide group 1 were able to specifically discriminate stomach cancer from the other cancers with high accuracy.

[0600] The number of the aforementioned polynucleotides with cancer type specificity in the combination can be 2, 3, 4, 5, 6, 7, 8, 9, 10 or more for the combination. The combinations of 6 or more of these polynucleotides were able to exhibit discriminant accuracy of 80% or higher.

[0601] Specifically, the discriminant accuracy of the measurement using the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 21 or a complementary sequence thereof is shown in Table 8-1. The measurement using the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 21 or a complementary sequence thereof exhibited the highest accuracy of 79.8% in the training cohort and accuracy of 83.8% in the validation cohort. Also, for example, the measurement using the combinations of two polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 21 or a complementary sequence thereof exhibited the highest accuracy of 82.4% in the training cohort and accuracy of 80.9% in the validation cohort. Furthermore, for example, the measurement using the combinations of three polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 21 or a complementary sequence thereof exhibited the highest accuracy of 84.1% in the training cohort and accuracy of 83.8% in the validation cohort. Furthermore, for example, the measurement using the combinations of four polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 21 or a complementary sequence thereof exhibited the highest accuracy of 85.9% in the training cohort and accuracy of 82.7% in the validation cohort. Furthermore, for example, the measurement using the combinations of five polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 21 or a complementary sequence thereof exhibited the highest accuracy of 87.9% in the training cohort and accuracy of 88.4% in the validation cohort. Furthermore, for example, the measurement using the combinations of six polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 21 or a complementary sequence thereof exhibited the highest accuracy of 87.0% in the training cohort and accuracy of 87.3% in the validation cohort.

[0602] Specifically, the discriminant accuracy of the measurement using the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 34 or a complementary sequence thereof is shown in Table 8-2. The measurement using the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 34 or a complementary sequence thereof exhibited the highest accuracy of 62.8% in the training cohort and accuracy of 60.7% in the validation cohort. Also, for example, the measurement using the combinations of two polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 34 or a complementary sequence thereof exhibited the highest accuracy of 81.0% in the training cohort and accuracy of 82.1% in the validation cohort. Furthermore, for example, the measurement using the combinations of three polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 34 or a complementary sequence thereof exhibited the highest accuracy of 84.4% in the training cohort and accuracy of 82.1% in the validation cohort. Furthermore, for example, the measurement using the combinations of four polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 34 or a complementary sequence thereof exhibited the highest accuracy of 87.0% in the training cohort and accuracy of 88.4% in the validation cohort. Furthermore, for example, the measurement using the combinations of five polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 34 or a complementary sequence thereof exhibited the highest accuracy of 88.2% in the training cohort and accuracy of 87.9% in the validation cohort. Furthermore, for example, the measurement using the combinations of six polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 34 or a complementary sequence thereof exhibited the highest accuracy of 87.3% in the training cohort and accuracy of 88.4% in the validation cohort.

[0603] Specifically, the discriminant accuracy of the measurement using the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 36 or a complementary sequence thereof is shown in Table 8-3. The measurement using the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 36 or a complementary sequence thereof exhibited the highest accuracy of 78.7% in the training cohort and accuracy of 78.6% in the validation cohort. Also, for example, the measurement using the combinations of two polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 36 or a complementary sequence thereof exhibited the highest accuracy of 82.7% in the training cohort and accuracy of 82.7% in the validation cohort. Furthermore, for example, the measurement using the combinations of three polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 36 or a complementary sequence thereof exhibited the highest accuracy of 85.0% in the training cohort and accuracy of 86.7% in the validation cohort. Furthermore, for example, the measurement using the combinations of four polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 36 or a complementary sequence thereof exhibited the highest accuracy of 87.0% in the training cohort and accuracy of 85.5% in the validation cohort. Furthermore, for example, the measurement using the combinations of five polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 36 or a complementary sequence thereof exhibited the highest accuracy of 87.9% in the training cohort and accuracy of 86.1% in the validation cohort. Furthermore, for example, the measurement using the combinations of six polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 36 or a complementary sequence thereof exhibited the highest accuracy of 87.3% in the training cohort and accuracy of 87.9% in the validation cohort.

[0604]  Specifically, the discriminant accuracy of the measurement using the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 98 or a complementary sequence thereof is shown in Table 8-4. The measurement using the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 98 or a complementary sequence thereof exhibited the highest accuracy of 70.9% in the training cohort and accuracy of 70.5% in the validation cohort. Also, for example, the measurement using the combinations of two polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 98 or a complementary sequence thereof exhibited the highest accuracy of 82.4% in the training cohort and accuracy of 82.1% in the validation cohort. Furthermore, for example, the measurement using the combinations of three polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 98 or a complementary sequence thereof exhibited the highest accuracy of 84.1% in the training cohort and accuracy of 85.5% in the validation cohort. Furthermore, for example, the measurement using the combinations of four polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 98 or a complementary sequence thereof exhibited the highest accuracy of 86.7% in the training cohort and accuracy of 89.6% in the validation cohort. Furthermore, for example, the measurement using the combinations of five polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 98 or a complementary sequence thereof exhibited the highest accuracy of 88.2% in the training cohort and accuracy of 87.9% in the validation cohort. Furthermore, for example, the measurement using the combinations of six polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 98 or a complementary sequence thereof exhibited the highest accuracy of 87.9% in the training cohort and accuracy of 88.4% in the validation cohort.

[0605] Specifically, the discriminant accuracy of the measurement using the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 155 or a complementary sequence thereof is shown in Table 8-5. The measurement using the polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 155 or a complementary sequence thereof exhibited the highest accuracy of 67.1% in the training cohort and accuracy of 69.9% in the validation cohort. Also, for example, the measurement using the combinations of two polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 155 or a complementary sequence thereof exhibited the highest accuracy of 81.6% in the training cohort and accuracy of 75.7% in the validation cohort. Furthermore, for example, the measurement using the combinations of three polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 155 or a complementary sequence thereof exhibited the highest accuracy of 84.4% in the training cohort and accuracy of 85.0% in the validation cohort. Furthermore, for example, the measurement using the combinations of four polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 155 or a complementary sequence thereof exhibited the highest accuracy of 87.0% in the training cohort and accuracy of 89.0% in the validation cohort. Furthermore, for example, the measurement using the combinations of five polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 155 or a complementary sequence thereof exhibited the highest accuracy of 88.2% in the training cohort and accuracy of 87.3% in the validation cohort. Furthermore, for example, the measurement using the combinations of six polynucleotides comprising at least one polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 155 or a complementary sequence thereof exhibited the highest accuracy of 88.2% in the training cohort and accuracy of 89.6% in the validation cohort.

[0606] The expression level measurement values of the nucleotide sequences represented by SEQ ID NOs: 9, 13, 143, 155, 194, and 639 were compared among 34 stomach cancer patients, 102 healthy subjects, 63 pancreatic cancer patients, 65 bile duct cancer patients, 35 colorectal cancer patients, 32 liver cancer patients, and 17 benign pancreaticobiliary disease patients in the training cohort. As a result, a scatter diagram that significantly separated the discriminant score of the stomach cancer patient group from the discriminant scores of the other groups was obtained in the training cohort (see the upper diagram of Figure 4). These results were also reproducible for the validation cohort (see the lower diagram of Figure 4).
[Table 8-1]
 Training cohortValidation cohort
SEQ ID NO:Accuracy (%)Sensitivity (%)Specificity (%)Accuracy (%)Sensitivity (%)Specificity (%)
21 79.8 82.4 79.6 83.8 81.2 84.1
9_21 82.4 97.1 80.8 80.9 81.2 80.9
9_21_34 84.1 91.2 83.4 83.8 75 84.7
9_21_34_36 85.9 91.2 85.3 82.7 68.8 84.1
9_21_34_36_98 87.9 97.1 86.9 88.4 81.2 89.2
9_21_36_98_130_637 83.6 100 81.8 85 87.5 84.7
9_21_34_36_98_637 87 94.1 86.3 87.3 87.5 87.3
9_21_34_36_98_155 86.7 97.1 85.6 89 81.2 89.8
21_36_75_98_155_635 83 97.1 81.5 87.9 87.5 87.9
9_21_36_98_108_155 86.7 100 85.3 86.7 81.2 87.3
[Table 8-2]
 Training cohortValidation cohort
SEQ ID NO:Accuracy (%)Sensitivity (%)Specificity (%)Accuracy (%)Sensitivity (%)Specificity (%)
34 62.8 67.6 62.3 60.7 81.2 58.6
21_34 81 82.4 80.8 82.1 81.2 82.2
9_34_36 84.4 94.1 83.4 82.1 68.8 83.4
9_34_36_98 87 97.1 85.9 88.4 87.5 88.5
9_34_36_98_635 88.2 97.1 87.2 87.9 87.5 87.9
34_36_143_155_187_635 86.2 94.1 85.3 86.1 87.5 86
9_34_36_66_98_187 87.3 97.1 86.3 88.4 81.2 89.2
9_34_36_98_187_637 86.5 94.1 85.6 87.3 87.5 87.3
9_34_36_98_185_637 86.7 97.1 85.6 86.7 87.5 86.6
9_34_36_98_637_639 86.5 97.1 85.3 87.9 87.5 87.9
[Table 8-3]
 Training cohortValidation cohort
SEQ ID NO:Accuracy (%)Sensitivity (%)Specificity (%)Accuracy (%)Sensitivity (%)Specificity (%)
36 78.7 82.4 78.3 78.6 81.2 78.3
9_36 82.7 97.1 81.2 82.7 75 83.4
9_36_98 85 100 83.4 86.7 87.5 86.6
9_36_75_98 87 100 85.6 85.5 81.2 86
9_13_36_108_194 87.9 94.1 87.2 86.1 75 87.3
9_36_98_108_638_639 85.6 94.1 84.7 88.4 87.5 88.5
36_98_155_194_635_642 85.3 100 83.7 86.1 81.2 86.6
9_34_36_75_98_637 87.3 97.1 86.3 87.9 87.5 87.9
21_36_98_155_185_635 83.9 97.1 82.4 89 87.5 89.2
9_36_98_108_155_635 85.9 97.1 84.7 87.3 81.2 87.9
[Table 8-4]
 Training cohortValidation cohort
SEQ ID NO:Accuracy (%)Sensitivity (%)Specificity (%)Accuracy (%)Sensitivity (%)Specificity (%)
98 70.9 64.7 71.6 70.5 62.5 71.3
36_98 82.4 88.2 81.8 82.1 75 82.8
9_98_639 84.1 91.2 83.4 85.5 81.2 86
9_36_98_194 86.7 97.1 85.6 89.6 81.2 90.4
9_98_130_135_639 88.2 97.1 87.2 87.9 100 86.6
9_36_98_130_194_637 87.3 100 85.9 89.6 87.5 89.8
21_36_98_108_155_635 85.6 94.1 84.7 89.6 87.5 89.8
9_36_98_108_155_639 87.9 97.1 86.9 88.4 87.5 88.5
9_36_98_155_187_639 87 97.1 85.9 88.4 93.8 87.9
9_36_98_155_187_637 85.9 100 84.3 85.5 81.2 86
[Table 8-5]
 Training cohortValidation cohort
SEQ ID NO:Accuracy (%)Sensitivity (%)Specificity (%)Accuracy (%)Sensitivity (%)Specificity (%)
155 67.1 58.8 68.1 69.9 75 69.4
9_155 81.6 94.1 80.2 75.7 75 75.8
9_155_639 84.4 97.1 83.1 85 87.5 84.7
9_130_155639 87 91.2 86.6 89 100 87.9
9_34_130_155_639 88.2 91.2 87.9 87.3 93.8 86.6
9_36_75_98_155_635 85.6 100 84 86.1 81.2 86.6
36_98_130_155_185_635 85.9 94.1 85 86.1 87.5 86
9_13_143_155_194_639 88.2 94.1 87.5 89.6 87.5 89.8
9_13_34_36_98_155 87 97.1 85.9 89 81.2 89.8
36_98_108_155_193_635 85.3 94.1 84.3 86.7 81.2 87.3

[Comparative Example 1]


<Stomach cancer discriminant performance of existing tumor markers in blood>



[0607] The concentrations of the existing tumor markers CEA and CA19-9 in blood were measured in the training cohort and the validation cohort obtained in the preceding Reference Examples. When the concentrations of these tumor markers in blood are higher than the reference values described in Kim, H.J. et al., Acta Oncologica, 2009, No. 48, p. 385 to 390 (CEA: 5 ng/mL, CA19-9: 37 U/mL), subjects are usually suspected of having cancer. Thus, whether or not the concentrations of CEA and CA19-9 in blood exceeded their reference values was confirmed for each sample, and the results were assessed for the ability of these tumor markers to detect cancer in stomach cancer patients. The sensitivity of each existing marker in the training cohort and the validation cohort was calculated. The results are shown in Table 5. The sensitivity of CEA and CA19-9 was as low as 2.9% in the training cohort, and was as low as 12.5% and 12.5%, respectively, in the validation cohort, demonstrating that neither of the markers are useful in the detection of stomach cancer (Table 5).

[0608] On the other hand, as shown above in Tables 3 and 6 of Examples 1 and 2, it can be concluded that in all of the polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 169 combinations of 1 or 2 polynucleotides exhibiting sensitivity beyond the existing stomach cancer markers are present, and thus such polynucleotides serve as excellent diagnosis markers.

[0609] As shown in these Examples and Comparative Example, the kit, etc., and the method of the present invention can detect stomach cancer with higher sensitivity than the existing tumor markers and therefore permit early detection and treatment of stomach cancer. As a result, improvement in survival rate resulting from reduction in the risk of recurrence, and a therapeutic option of stomach-conserving therapy can also be provided.

Industrial Applicability



[0610] According to the present invention, stomach cancer can be effectively detected by a simple and inexpensive method. This enables early detection, diagnosis and treatment of stomach cancer. The method of the present invention can detect stomach cancer with limited invasiveness using the blood of a patient and therefore allows stomach cancer to be detected conveniently and rapidly.

SEQUENCE LISTING



[0611] 

<110> Toray Industries, Inc. National Cancer Center

<120> Kit and method for detecting stomach cancer

<130> PH-6236-PCT

<150> JP 2014-123224
<151> 2014-06-16

<150> JP 2015-071485
<151> 2015-03-31

<160> 657

<170> PatentIn version 3.5

<210> 1
<211> 18
<212> RNA
<213> Homo sapiens

<400> 1
ccagaggugg ggacugag   18

<210> 2
<211> 21
<212> RNA
<213> Homo sapiens

<400> 2
cgggagcugg ggucugcagg u   21

<210> 3
<211> 22
<212> RNA
<213> Homo sapiens

<400> 3
cuccuggggc ccgcacucuc gc   22

<210> 4
<211> 24
<212> RNA
<213> Homo sapiens

<400> 4
ccccgggaac gucgagacug gagc   24

<210> 5
<211> 22
<212> RNA
<213> Homo sapiens

<400> 5
uggcgggggu agagcuggcu gc   22

<210> 6
<211> 21
<212> RNA
<213> Homo sapiens

<400> 6
ugagggaccc aggacaggag a   21

<210> 7
<211> 22
<212> RNA
<213> Homo sapiens

<400> 7
ugagccccug ugccgccccc ag   22

<210> 8
<211> 22
<212> RNA
<213> Homo sapiens

<400> 8
ucaaaaucag gagucggggc uu   22

<210> 9
<211> 21
<212> RNA
<213> Homo sapiens

<400> 9
cgggccggag gucaagggcg u   21

<210> 10
<211> 21
<212> RNA
<213> Homo sapiens

<400> 10
agcggugcuc cugcgggccg a   21

<210> 11
<211> 21
<212> RNA
<213> Homo sapiens

<400> 11
cggcggggac ggcgauuggu c   21

<210> 12
<211> 23
<212> RNA
<213> Homo sapiens

<400> 12
aggguggggc uggagguggg gcu   23

<210> 13
<211> 21
<212> RNA
<213> Homo sapiens

<400> 13
gcugggaagg caaagggacg u   21

<210> 14
<211> 20
<212> RNA
<213> Homo sapiens

<400> 14
cggggugggu gaggucgggc   20

<210> 15
<211> 22
<212> RNA
<213> Homo sapiens

<400> 15
uagggauggg aggccaggau ga   22

<210> 16
<211> 22
<212> RNA
<213> Homo sapiens

<400> 16
uggggaggug uggagucagc au   22

<210> 17
<211> 21
<212> RNA
<213> Homo sapiens

<400> 17
guguggccgg caggcgggug g   21

<210> 18
<211> 18
<212> RNA
<213> Homo sapiens

<400> 18
cggugagcgc ucgcuggc   18

<210> 19
<211> 19
<212> RNA
<213> Homo sapiens

<400> 19
uugaucucgg aagcuaagc   19

<210> 20
<211> 23
<212> RNA
<213> Homo sapiens

<400> 20
agaggcuuug ugcggauacg ggg   23

<210> 21
<211> 23
<212> RNA
<213> Homo sapiens

<400> 21
ucgaggacug guggaagggc cuu   23

<210> 22
<211> 23
<212> RNA
<213> Homo sapiens

<400> 22
uggggaaggc uuggcaggga aga   23

<210> 23
<211> 23
<212> RNA
<213> Homo sapiens

<400> 23
ggaugguugg gggcggucgg cgu   23

<210> 24
<211> 22
<212> RNA
<213> Homo sapiens

<400> 24
gcccaggacu uugugcgggg ug   22

<210> 25
<211> 20
<212> RNA
<213> Homo sapiens

<400> 25
ggcggcgggg agguaggcag   20

<210> 26
<211> 22
<212> RNA
<213> Homo sapiens

<400> 26
agugggaggc cagggcacgg ca   22

<210> 27
<211> 23
<212> RNA
<213> Homo sapiens

<400> 27
uggggggaca gauggagagg aca   23

<210> 28
<211> 20
<212> RNA
<213> Homo sapiens

<400> 28
gugucugggc ggacagcugc   20

<210> 29
<211> 21
<212> RNA
<213> Homo sapiens

<400> 29
guuggggugc aggggucugc u   21

<210> 30
<211> 23
<212> RNA
<213> Homo sapiens

<400> 30
cgagggguag aagagcacag ggg   23

<210> 31
<211> 20
<212> RNA
<213> Homo sapiens

<400> 31
gccggggcuu ugggugaggg   20

<210> 32
<211> 22
<212> RNA
<213> Homo sapiens

<400> 32
ccccuggggc ugggcaggcg ga   22

<210> 33
<211> 22
<212> RNA
<213> Homo sapiens

<400> 33
ucgggccugg gguuggggga gc   22

<210> 34
<211> 22
<212> RNA
<213> Homo sapiens

<400> 34
gugggugcug gugggagccg ug   22

<210> 35
<211> 23
<212> RNA
<213> Homo sapiens

<400> 35
cggggccgua gcacugucug aga   23

<210> 36
<211> 18
<212> RNA
<213> Homo sapiens

<400> 36
gaggcugaag gaagaugg   18

<210> 37
<211> 22
<212> RNA
<213> Homo sapiens

<400> 37
ccgggagaag gagguggccu gg   22

<210> 38
<211> 24
<212> RNA
<213> Homo sapiens

<400> 38
ugaggggccu cagaccgagc uuuu   24

<210> 39
<211> 23
<212> RNA
<213> Homo sapiens

<400> 39
ugaggauaug gcagggaagg gga   23

<210> 40
<211> 21
<212> RNA
<213> Homo sapiens

<400> 40
ugggggugug gggagagaga g   21

<210> 41
<211> 17
<212> RNA
<213> Homo sapiens

<400> 41
gggagaaggg ucggggc   17

<210> 42
<211> 22
<212> RNA
<213> Homo sapiens

<400> 42
aggcgaugug gggauguaga ga   22

<210> 43
<211> 23
<212> RNA
<213> Homo sapiens

<400> 43
ucaauaggaa agagguggga ccu   23

<210> 44
<211> 21
<212> RNA
<213> Homo sapiens

<400> 44
caggaguggg gggugggacg u   21

<210> 45
<211> 22
<212> RNA
<213> Homo sapiens

<400> 45
cuucccccca guaaucuuca uc   22

<210> 46
<211> 22
<212> RNA
<213> Homo sapiens

<400> 46
ggcuggagcg agugcagugg ug   22

<210> 47
<211> 22
<212> RNA
<213> Homo sapiens

<400> 47
caggcacggg agcucaggug ag   22

<210> 48
<211> 22
<212> RNA
<213> Homo sapiens

<400> 48
gggacccagg gagagacgua ag   22

<210> 49
<211> 22
<212> RNA
<213> Homo sapiens

<400> 49
uggcggcggu aguuaugggc uu   22

<210> 50
<211> 22
<212> RNA
<213> Homo sapiens

<400> 50
uuggggauug ggucaggcca gu   22

<210> 51
<211> 20
<212> RNA
<213> Homo sapiens

<400> 51
ucucuucauc uaccccccag   20

<210> 52
<211> 22
<212> RNA
<213> Homo sapiens

<400> 52
guggguacgg cccagugggg gg   22

<210> 53
<211> 22
<212> RNA
<213> Homo sapiens

<400> 53
ggcuacaaca caggacccgg gc   22

<210> 54
<211> 23
<212> RNA
<213> Homo sapiens

<400> 54
agaagaaggc ggucggucug cgg   23

<210> 55
<211> 22
<212> RNA
<213> Homo sapiens

<400> 55
agacacauuu ggagagggac cc   22

<210> 56
<211> 22
<212> RNA
<213> Homo sapiens

<400> 56
acgcccuucc cccccuucuu ca   22

<210> 57
<211> 22
<212> RNA
<213> Homo sapiens

<400> 57
ugcggggcua gggcuaacag ca   22

<210> 58
<211> 17
<212> RNA
<213> Homo sapiens

<400> 58
gccggacaag agggagg   17

<210> 59
<211> 20
<212> RNA
<213> Homo sapiens

<400> 59
ucacaccugc cucgcccccc   20

<210> 60
<211> 24
<212> RNA
<213> Homo sapiens

<400> 60
uggggagcug aggcucuggg ggug   24

<210> 61
<211> 19
<212> RNA
<213> Homo sapiens

<400> 61
cggggccaga gcagagagc   19

<210> 62
<211> 22
<212> RNA
<213> Homo sapiens

<400> 62
gugaacgggc gccaucccga gg   22

<210> 63
<211> 21
<212> RNA
<213> Homo sapiens

<400> 63
aagggacagg gagggucgug g   21

<210> 64
<211> 22
<212> RNA
<213> Homo sapiens

<400> 64
ugggcgaggg cggcugagcg gc   22

<210> 65
<211> 23
<212> RNA
<213> Homo sapiens

<400> 65
gagggcagcg uggguguggc gga   23

<210> 66
<211> 22
<212> RNA
<213> Homo sapiens

<400> 66
gggggucccc ggugcucgga uc   22

<210> 67
<211> 23
<212> RNA
<213> Homo sapiens

<400> 67
cugggcccgc ggcgggcgug ggg   23

<210> 68
<211> 23
<212> RNA
<213> Homo sapiens

<400> 68
ugggagggga gaggcagcaa gca   23

<210> 69
<211> 20
<212> RNA
<213> Homo sapiens

<400> 69
uagggggugg caggcuggcc   20

<210> 70
<211> 21
<212> RNA
<213> Homo sapiens

<400> 70
uggggcgggg caggucccug c   21

<210> 71
<211> 22
<212> RNA
<213> Homo sapiens

<400> 71
caggaggcag ugggcgagca gg   22

<210> 72
<211> 20
<212> RNA
<213> Homo sapiens

<400> 72
agagaugaag cgggggggcg   20

<210> 73
<211> 18
<212> RNA
<213> Homo sapiens

<400> 73
auccuaguca cggcacca   18

<210> 74
<211> 23
<212> RNA
<213> Homo sapiens

<400> 74
ggaggcgcag gcucggaaag gcg   23

<210> 75
<211> 20
<212> RNA
<213> Homo sapiens

<400> 75
gcggaaggcg gagcggcgga   20

<210> 76
<211> 21
<212> RNA
<213> Homo sapiens

<400> 76
acaggagugg gggugggaca u   21

<210> 77
<211> 23
<212> RNA
<213> Homo sapiens

<400> 77
cucggggcag gcggcuggga gcg   23

<210> 78
<211> 25
<212> RNA
<213> Homo sapiens

<400> 78
agcggggagg aagugggcgc ugcuu   25

<210> 79
<211> 21
<212> RNA
<213> Homo sapiens

<400> 79
cguggaggac gaggaggagg c   21

<210> 80
<211> 23
<212> RNA
<213> Homo sapiens

<400> 80
uugcucugcu cccccgcccc cag   23

<210> 81
<211> 22
<212> RNA
<213> Homo sapiens

<400> 81
ugauugucuu cccccacccu ca   22

<210> 82
<211> 22
<212> RNA
<213> Homo sapiens

<400> 82
ucugcccccu ccgcugcugc ca   22

<210> 83
<211> 24
<212> RNA
<213> Homo sapiens

<400> 83
ugggcgaggg gugggcucuc agag   24

<210> 84
<211> 23
<212> RNA
<213> Homo sapiens

<400> 84
gacacgggcg acagcugcgg ccc   23

<210> 85
<211> 23
<212> RNA
<213> Homo sapiens

<400> 85
ugagcaccac acaggccggg cgc   23

<210> 86
<211> 21
<212> RNA
<213> Homo sapiens

<400> 86
caggcaggug uaggguggag c   21

<210> 87
<211> 22
<212> RNA
<213> Homo sapiens

<400> 87
acuggguagg uggggcucca gg   22

<210> 88
<211> 22
<212> RNA
<213> Homo sapiens

<400> 88
cgucccgggg cugcgcgagg ca   22

<210> 89
<211> 22
<212> RNA
<213> Homo sapiens

<400> 89
uggggguggu cucuagccaa gg   22

<210> 90
<211> 20
<212> RNA
<213> Homo sapiens

<400> 90
ggauccgagu cacggcacca   20

<210> 91
<211> 21
<212> RNA
<213> Homo sapiens

<400> 91
auccaguucu cugagggggc u   21

<210> 92
<211> 22
<212> RNA
<213> Homo sapiens

<400> 92
gguggcccgg ccgugccuga gg   22

<210> 93
<211> 25
<212> RNA
<213> Homo sapiens

<400> 93
gugaggcggg gccaggaggg ugugu   25

<210> 94
<211> 22
<212> RNA
<213> Homo sapiens

<400> 94
agacugacgg cuggaggccc au   22

<210> 95
<211> 23
<212> RNA
<213> Homo sapiens

<400> 95
gaacgccugu ucuugccagg ugg   23

<210> 96
<211> 22
<212> RNA
<213> Homo sapiens

<400> 96
ugggagggcg uggaugaugg ug   22

<210> 97
<211> 23
<212> RNA
<213> Homo sapiens

<400> 97
acggggaguc aggcaguggu gga   23

<210> 98
<211> 21
<212> RNA
<213> Homo sapiens

<400> 98
aaggcagggc ccccgcuccc c   21

<210> 99
<211> 23
<212> RNA
<213> Homo sapiens

<400> 99
cgggcugucc ggaggggucg gcu   23

<210> 100
<211> 19
<212> RNA
<213> Homo sapiens

<400> 100
ugggggagau ggggguuga   19

<210> 101
<211> 19
<212> RNA
<213> Homo sapiens

<400> 101
ggcuggucag augggagug   19

<210> 102
<211> 22
<212> RNA
<213> Homo sapiens

<400> 102
cugguacagg ccugggggac ag   22

<210> 103
<211> 23
<212> RNA
<213> Homo sapiens

<400> 103
gccccggcgc gggcggguuc ugg   23

<210> 104
<211> 20
<212> RNA
<213> Homo sapiens

<400> 104
ccccagggcg acgcggcggg   20

<210> 105
<211> 23
<212> RNA
<213> Homo sapiens

<400> 105
acaggcggcu guagcaaugg ggg   23

<210> 106
<211> 20
<212> RNA
<213> Homo sapiens

<400> 106
gugagucagg guggggcugg   20

<210> 107
<211> 17
<212> RNA
<213> Homo sapiens

<400> 107
uuggaggcgu ggguuuu   17

<210> 108
<211> 22
<212> RNA
<213> Homo sapiens

<400> 108
ggaggggucc cgcacuggga gg   22

<210> 109
<211> 22
<212> RNA
<213> Homo sapiens

<400> 109
gugggcuggg cugggcuggg cc   22

<210> 110
<211> 20
<212> RNA
<213> Homo sapiens

<400> 110
cgggcguggu ggugggggug   20

<210> 111
<211> 17
<212> RNA
<213> Homo sapiens

<400> 111
guggggccag gcggugg   17

<210> 112
<211> 22
<212> RNA
<213> Homo sapiens

<400> 112
ugguggagga agagggcagc uc   22

<210> 113
<211> 18
<212> RNA
<213> Homo sapiens

<400> 113
ggugggcuuc ccggaggg   18

<210> 114
<211> 20
<212> RNA
<213> Homo sapiens

<400> 114
cuaggugggg ggcuugaagc   20

<210> 115
<211> 21
<212> RNA
<213> Homo sapiens

<400> 115
agguggguau ggaggagccc u   21

<210> 116
<211> 22
<212> RNA
<213> Homo sapiens

<400> 116
aggcggggcg ccgcgggacc gc   22

<210> 117
<211> 23
<212> RNA
<213> Homo sapiens

<400> 117
ugggcagggg cuuauuguag gag   23

<210> 118
<211> 17
<212> RNA
<213> Homo sapiens

<400> 118
ccccggggag cccggcg   17

<210> 119
<211> 18
<212> RNA
<213> Homo sapiens

<400> 119
uucccagcca acgcacca   18

<210> 120
<211> 22
<212> RNA
<213> Homo sapiens

<400> 120
agggacggga cgcggugcag ug   22

<210> 121
<211> 20
<212> RNA
<213> Homo sapiens

<400> 121
acucaaacug ugggggcacu   20

<210> 122
<211> 18
<212> RNA
<213> Homo sapiens

<400> 122
gugaaggccc ggcggaga   18

<210> 123
<211> 22
<212> RNA
<213> Homo sapiens

<400> 123
gcugcgggcu gcggucaggg cg   22

<210> 124
<211> 26
<212> RNA
<213> Homo sapiens

<400> 124
cucggccgcg gcgcguagcc cccgcc   26

<210> 125
<211> 23
<212> RNA
<213> Homo sapiens

<400> 125
ugaggggcag agagcgagac uuu   23

<210> 126
<211> 22
<212> RNA
<213> Homo sapiens

<400> 126
cucggcgcgg ggcgcgggcu cc   22

<210> 127
<211> 22
<212> RNA
<213> Homo sapiens

<400> 127
ggggcuguga uugaccagca gg   22

<210> 128
<211> 22
<212> RNA
<213> Homo sapiens

<400> 128
accuugccuu gcugcccggg cc   22

<210> 129
<211> 20
<212> RNA
<213> Homo sapiens

<400> 129
ugggaauggg gguaagggcc   20

<210> 130
<211> 21
<212> RNA
<213> Homo sapiens

<400> 130
cuuccgcccc gccgggcguc g   21

<210> 131
<211> 18
<212> RNA
<213> Homo sapiens

<400> 131
gggucccggg gagggggg   18

<210> 132
<211> 19
<212> RNA
<213> Homo sapiens

<400> 132
ugcggcagag cugggguca   19

<210> 133
<211> 24
<212> RNA
<213> Homo sapiens

<400> 133
uggggggaca ggaugagagg cugu   24

<210> 134
<211> 21
<212> RNA
<213> Homo sapiens

<400> 134
cugggagggg cuggguuugg c   21

<210> 135
<211> 21
<212> RNA
<213> Homo sapiens

<400> 135
cuggggggag gagacccugc u   21

<210> 136
<211> 23
<212> RNA
<213> Homo sapiens

<400> 136
ccagggggau gggcgagcuu ggg   23

<210> 137
<211> 20
<212> RNA
<213> Homo sapiens

<400> 137
ugugggacug caaaugggag   20

<210> 138
<211> 22
<212> RNA
<213> Homo sapiens

<400> 138
ggggaacugu agaugaaaag gc   22

<210> 139
<211> 21
<212> RNA
<213> Homo sapiens

<400> 139
ucaccuggcu ggcccgccca g   21

<210> 140
<211> 19
<212> RNA
<213> Homo sapiens

<400> 140
agcagggcug gggauugca   19

<210> 141
<211> 17
<212> RNA
<213> Homo sapiens

<400> 141
ggggcugggc gcgcgcc   17

<210> 142
<211> 22
<212> RNA
<213> Homo sapiens

<400> 142
ucggccuggg gaggaggaag gg   22

<210> 143
<211> 17
<212> RNA
<213> Homo sapiens

<400> 143
cgcgccgggc ccggguu   17

<210> 144
<211> 19
<212> RNA
<213> Homo sapiens

<400> 144
uggggcggag cuuccggag   19

<210> 145
<211> 22
<212> RNA
<213> Homo sapiens

<400> 145
gaggguuggg uggaggcucu cc   22

<210> 146
<211> 19
<212> RNA
<213> Homo sapiens

<400> 146
aggcacggug ucagcaggc   19

<210> 147
<211> 18
<212> RNA
<213> Homo sapiens

<400> 147
cgggcguggu gguggggg   18

<210> 148
<211> 23
<212> RNA
<213> Homo sapiens

<400> 148
ugggggcugg gaugggccau ggu   23

<210> 149
<211> 22
<212> RNA
<213> Homo sapiens

<400> 149
ggggcugggg ccggggccga gc   22

<210> 150
<211> 19
<212> RNA
<213> Homo sapiens

<400> 150
ggggccuggc ggugggcgg   19

<210> 151
<211> 21
<212> RNA
<213> Homo sapiens

<400> 151
cccggagcca ggaugcagcu c   21

<210> 152
<211> 19
<212> RNA
<213> Homo sapiens

<400> 152
aucccaccac ugccaccau   19

<210> 153
<211> 22
<212> RNA
<213> Homo sapiens

<400> 153
caggaaggau uuagggacag gc   22

<210> 154
<211> 25
<212> RNA
<213> Homo sapiens

<400> 154
aggggggcac ugcgcaagca aagcc   25

<210> 155
<211> 23
<212> RNA
<213> Homo sapiens

<400> 155
uggugggugg ggaggagaag ugc   23

<210> 156
<211> 21
<212> RNA
<213> Homo sapiens

<400> 156
aucacauugc cagggauuac c   21

<210> 157
<211> 22
<212> RNA
<213> Homo sapiens

<400> 157
uggggagcgg cccccgggug gg   22

<210> 158
<211> 20
<212> RNA
<213> Homo sapiens

<400> 158
cgcgggucgg ggucugcagg   20

<210> 159
<211> 22
<212> RNA
<213> Homo sapiens

<400> 159
uaggggcagc agaggaccug gg   22

<210> 160
<211> 17
<212> RNA
<213> Homo sapiens

<400> 160
accccacucc ugguacc   17

<210> 161
<211> 23
<212> RNA
<213> Homo sapiens

<400> 161
ugggccaggg agcagcuggu ggg   23

<210> 162
<211> 25
<212> RNA
<213> Homo sapiens

<400> 162
aagggaggag gagcggaggg gcccu   25

<210> 163
<211> 18
<212> RNA
<213> Homo sapiens

<400> 163
aucccaccuc ugccacca   18

<210> 164
<211> 17
<212> RNA
<213> Homo sapiens

<400> 164
cucagugacu caugugc   17

<210> 165
<211> 20
<212> RNA
<213> Homo sapiens

<400> 165
ugggaggagg ggaucuuggg   20

<210> 166
<211> 23
<212> RNA
<213> Homo sapiens

<400> 166
gggggccgau acacuguacg aga   23

<210> 167
<211> 22
<212> RNA
<213> Homo sapiens

<400> 167
acaggugagg uucuugggag cc   22

<210> 168
<211> 22
<212> RNA
<213> Homo sapiens

<400> 168
ggguggggau uuguugcauu ac   22

<210> 169
<211> 21
<212> RNA
<213> Homo sapiens

<400> 169
cggggcagcu caguacagga u   21

<210> 170
<211> 18
<212> RNA
<213> Homo sapiens

<400> 170
cggggcggca ggggccuc   18

<210> 171
<211> 21
<212> RNA
<213> Homo sapiens

<400> 171
gcagggacag caaaggggug c   21

<210> 172
<211> 19
<212> RNA
<213> Homo sapiens

<400> 172
gggggaagaa aaggugggg   19

<210> 173
<211> 23
<212> RNA
<213> Homo sapiens

<400> 173
aggagguggu acuaggggcc agc   23

<210> 174
<211> 21
<212> RNA
<213> Homo sapiens

<400> 174
agggagggac gggggcugug c   21

<210> 175
<211> 22
<212> RNA
<213> Homo sapiens

<400> 175
acuggggagc agaaggagaa cc   22

<210> 176
<211> 22
<212> RNA
<213> Homo sapiens

<400> 176
uauagggauu ggagccgugg cg   22

<210> 177
<211> 17
<212> RNA
<213> Homo sapiens

<400> 177
gcugggcgag gcuggca   17

<210> 178
<211> 22
<212> RNA
<213> Homo sapiens

<400> 178
agggggcgca gucacugacg ug   22

<210> 179
<211> 22
<212> RNA
<213> Homo sapiens

<400> 179
uggggaaggc gucagugucg gg   22

<210> 180
<211> 22
<212> RNA
<213> Homo sapiens

<400> 180
cagcagggga gagagaggag uc   22

<210> 181
<211> 24
<212> RNA
<213> Homo sapiens

<400> 181
agggcuggac ucagcggcgg agcu   24

<210> 182
<211> 22
<212> RNA
<213> Homo sapiens

<400> 182
uccaggcagg agccggacug ga   22

<210> 183
<211> 18
<212> RNA
<213> Homo sapiens

<400> 183
gggugcgggc cggcgggg   18

<210> 184
<211> 21
<212> RNA
<213> Homo sapiens

<400> 184
aucacauugc cagggauuuc c   21

<210> 185
<211> 17
<212> RNA
<213> Homo sapiens

<400> 185
ggcgggugcg ggggugg   17

<210> 186
<211> 25
<212> RNA
<213> Homo sapiens

<400> 186
uagggguggg ggaauucagg ggugu   25

<210> 187
<211> 22
<212> RNA
<213> Homo sapiens

<400> 187
uugaggagac augguggggg cc   22

<210> 188
<211> 22
<212> RNA
<213> Homo sapiens

<400> 188
aaaccguuac cauuacugag uu   22

<210> 189
<211> 22
<212> RNA
<213> Homo sapiens

<400> 189
cagggcuggc agugacaugg gu   22

<210> 190
<211> 22
<212> RNA
<213> Homo sapiens

<400> 190
uggggcggag cuuccggagg cc   22

<210> 191
<211> 22
<212> RNA
<213> Homo sapiens

<400> 191
agacacauuu ggagagggaa cc   22

<210> 192
<211> 23
<212> RNA
<213> Homo sapiens

<400> 192
ucggggaguc ugggguccgg aau   23

<210> 193
<211> 17
<212> RNA
<213> Homo sapiens

<400> 193
ggggcgcggc cggaucg   17

<210> 194
<211> 23
<212> RNA
<213> Homo sapiens

<400> 194
cugggggacg cgugagcgcg agc   23

<210> 195
<211> 22
<212> RNA
<213> Homo sapiens

<400> 195
ugcagggguc gggugggcca gg   22

<210> 196
<211> 22
<212> RNA
<213> Homo sapiens

<400> 196
cugggagagg guuguuuacu cc   22

<210> 197
<211> 20
<212> RNA
<213> Homo sapiens

<400> 197
cuggguuggg cugggcuggg   20

<210> 198
<211> 19
<212> RNA
<213> Homo sapiens

<400> 198
gagggcgggu ggaggagga   19

<210> 199
<211> 20
<212> RNA
<213> Homo sapiens

<400> 199
ccugagcccg ggccgcgcag   20

<210> 200
<211> 86
<212> RNA
<213> Homo sapiens

<400> 200

<210> 201
<211> 61
<212> RNA
<213> Homo sapiens

<400> 201

<210> 202
<211> 84
<212> RNA
<213> Homo sapiens

<400> 202

<210> 203
<211> 136
<212> RNA
<213> Homo sapiens

<400> 203

<210> 204
<211> 61
<212> RNA
<213> Homo sapiens

<400> 204

<210> 205
<211> 72
<212> RNA
<213> Homo sapiens

<400> 205

<210> 206
<211> 90
<212> RNA
<213> Homo sapiens

<400> 206

<210> 207
<211> 81
<212> RNA
<213> Homo sapiens

<400> 207

<210> 208
<211> 64
<212> RNA
<213> Homo sapiens

<400> 208

<210> 209
<211> 71
<212> RNA
<213> Homo sapiens

<400> 209

<210> 210
<211> 80
<212> RNA
<213> Homo sapiens

<400> 210

<210> 211
<211> 63
<212> RNA
<213> Homo sapiens

<400> 211

<210> 212
<211> 110
<212> RNA
<213> Homo sapiens

<400> 212

<210> 213
<211> 73
<212> RNA
<213> Homo sapiens

<400> 213

<210> 214
<211> 69
<212> RNA
<213> Homo sapiens

<400> 214

<210> 215
<211> 66
<212> RNA
<213> Homo sapiens

<400> 215

<210> 216
<211> 87
<212> RNA
<213> Homo sapiens

<400> 216

<210> 217
<211> 74
<212> RNA
<213> Homo sapiens

<400> 217

<210> 218
<211> 61
<212> RNA
<213> Homo sapiens

<400> 218

<210> 219
<211> 53
<212> RNA
<213> Homo sapiens

<400> 219
guuugaucuc ggaagcuaag cagggucggg ccugguuagu acuuggaugg gag   53

<210> 220
<211> 85
<212> RNA
<213> Homo sapiens

<400> 220

<210> 221
<211> 63
<212> RNA
<213> Homo sapiens

<400> 221

<210> 222
<211> 79
<212> RNA
<213> Homo sapiens

<400> 222

<210> 223
<211> 86
<212> RNA
<213> Homo sapiens

<400> 223

<210> 224
<211> 71
<212> RNA
<213> Homo sapiens

<400> 224

<210> 225
<211> 80
<212> RNA
<213> Homo sapiens

<400> 225

<210> 226
<211> 82
<212> RNA
<213> Homo sapiens

<400> 226

<210> 227
<211> 82
<212> RNA
<213> Homo sapiens

<400> 227

<210> 228
<211> 65
<212> RNA
<213> Homo sapiens

<400> 228

<210> 229
<211> 92
<212> RNA
<213> Homo sapiens

<400> 229

<210> 230
<211> 137
<212> RNA
<213> Homo sapiens

<400> 230

<210> 231
<211> 64
<212> RNA
<213> Homo sapiens

<400> 231

<210> 232
<211> 67
<212> RNA
<213> Homo sapiens

<400> 232

<210> 233
<211> 67
<212> RNA
<213> Homo sapiens

<400> 233

<210> 234
<211> 69
<212> RNA
<213> Homo sapiens

<400> 234

<210> 235
<211> 63
<212> RNA
<213> Homo sapiens

<400> 235



<210> 236
<211> 82
<212> RNA
<213> Homo sapiens

<400> 236

<210> 237
<211> 68
<212> RNA
<213> Homo sapiens

<400> 237

<210> 238
<211> 63
<212> RNA
<213> Homo sapiens

<400> 238

<210> 239
<211> 75
<212> RNA
<213> Homo sapiens

<400> 239

<210> 240
<211> 68
<212> RNA
<213> Homo sapiens

<400> 240

<210> 241
<211> 86
<212> RNA
<213> Homo sapiens

<400> 241

<210> 242
<211> 86
<212> RNA
<213> Homo sapiens

<400> 242

<210> 243
<211> 73
<212> RNA
<213> Homo sapiens

<400> 243

<210> 244
<211> 98
<212> RNA
<213> Homo sapiens

<400> 244

<210> 245
<211> 102
<212> RNA
<213> Homo sapiens

<400> 245

<210> 246
<211> 68
<212> RNA
<213> Homo sapiens

<400> 246

<210> 247
<211> 83
<212> RNA
<213> Homo sapiens

<400> 247

<210> 248
<211> 76
<212> RNA
<213> Homo sapiens

<400> 248

<210> 249
<211> 63
<212> RNA
<213> Homo sapiens

<400> 249

<210> 250
<211> 93
<212> RNA
<213> Homo sapiens

<400> 250

<210> 251
<211> 57
<212> RNA
<213> Homo sapiens

<400> 251
cauuggaggg uguggaagac aucugggcca acucugaucu cuucaucuac cccccag   57

<210> 252
<211> 109
<212> RNA
<213> Homo sapiens

<400> 252

<210> 253
<211> 68
<212> RNA
<213> Homo sapiens

<400> 253

<210> 254
<211> 77
<212> RNA
<213> Homo sapiens

<400> 254

<210> 255
<211> 66
<212> RNA
<213> Homo sapiens

<400> 255

<210> 256
<211> 98
<212> RNA
<213> Homo sapiens

<400> 256

<210> 257
<211> 67
<212> RNA
<213> Homo sapiens

<400> 257

<210> 258
<211> 73
<212> RNA
<213> Homo sapiens

<400> 258

<210> 259
<211> 82
<212> RNA
<213> Homo sapiens

<400> 259

<210> 260
<211> 61
<212> RNA
<213> Homo sapiens

<400> 260

<210> 261
<211> 79
<212> RNA
<213> Homo sapiens

<400> 261

<210> 262
<211> 99
<212> RNA
<213> Homo sapiens

<400> 262

<210> 263
<211> 65
<212> RNA
<213> Homo sapiens

<400> 263

<210> 264
<211> 61
<212> RNA
<213> Homo sapiens

<400> 264

<210> 265
<211> 96
<212> RNA
<213> Homo sapiens

<400> 265

<210> 266
<211> 92
<212> RNA
<213> Homo sapiens

<400> 266

<210> 267
<211> 67
<212> RNA
<213> Homo sapiens

<400> 267

<210> 268
<211> 60
<212> RNA
<213> Homo sapiens

<400> 268
aggccuaggg gguggcaggc uggccaucag ugugggcuaa cccuguccuc ucccucccag   60

<210> 269
<211> 66
<212> RNA
<213> Homo sapiens

<400> 269

<210> 270
<211> 74
<212> RNA
<213> Homo sapiens

<400> 270

<210> 271
<211> 51
<212> RNA
<213> Homo sapiens

<400> 271
agagaugaag cgggggggcg gggucuugcu cuauugccua cgcugaucuc a   51

<210> 272
<211> 68
<212> RNA
<213> Homo sapiens

<400> 272

<210> 273
<211> 73
<212> RNA
<213> Homo sapiens

<400> 273

<210> 274
<211> 96
<212> RNA
<213> Homo sapiens

<400> 274

<210> 275
<211> 81
<212> RNA
<213> Homo sapiens

<400> 275

<210> 276
<211> 65
<212> RNA
<213> Homo sapiens

<400> 276

<210> 277
<211> 82
<212> RNA
<213> Homo sapiens

<400> 277

<210> 278
<211> 103
<212> RNA
<213> Homo sapiens

<400> 278

<210> 279
<211> 62
<212> RNA
<213> Homo sapiens

<400> 279

<210> 280
<211> 72
<212> RNA
<213> Homo sapiens

<400> 280

<210> 281
<211> 80
<212> RNA
<213> Homo sapiens

<400> 281

<210> 282
<211> 64
<212> RNA
<213> Homo sapiens

<400> 282

<210> 283
<211> 98
<212> RNA
<213> Homo sapiens

<400> 283

<210> 284
<211> 97
<212> RNA
<213> Homo sapiens

<400> 284

<210> 285
<211> 69
<212> RNA
<213> Homo sapiens

<400> 285

<210> 286
<211> 64
<212> RNA
<213> Homo sapiens

<400> 286

<210> 287
<211> 66
<212> RNA
<213> Homo sapiens

<400> 287

<210> 288
<211> 65
<212> RNA
<213> Homo sapiens

<400> 288

<210> 289
<211> 55
<212> RNA
<213> Homo sapiens

<400> 289
ccggauccga gucacggcac caaauuucau gcguguccgu gugaagagac cacca   55

<210> 290
<211> 115
<212> RNA
<213> Homo sapiens

<400> 290

<210> 291
<211> 115
<212> RNA
<213> Homo sapiens

<400> 291

<210> 292
<211> 87
<212> RNA
<213> Homo sapiens

<400> 292

<210> 293
<211> 86
<212> RNA
<213> Homo sapiens

<400> 293



<210> 294
<211> 90
<212> RNA
<213> Homo sapiens

<400> 294

<210> 295
<211> 81
<212> RNA
<213> Homo sapiens

<400> 295

<210> 296
<211> 66
<212> RNA
<213> Homo sapiens

<400> 296

<210> 297
<211> 94
<212> RNA
<213> Homo sapiens

<400> 297

<210> 298
<211> 90
<212> RNA
<213> Homo sapiens

<400> 298

<210> 299
<211> 60
<212> RNA
<213> Homo sapiens

<400> 299
caaggugggg gagauggggg uugaacuuca uuucucaugc ucauccccau cuccuuucag   60

<210> 300
<211> 109
<212> RNA
<213> Homo sapiens

<400> 300

<210> 301
<211> 84
<212> RNA
<213> Homo sapiens

<400> 301

<210> 302
<211> 80
<212> RNA
<213> Homo sapiens

<400> 302

<210> 303
<211> 80
<212> RNA
<213> Homo sapiens

<400> 303

<210> 304
<211> 106
<212> RNA
<213> Homo sapiens

<400> 304

<210> 305
<211> 86
<212> RNA
<213> Homo sapiens

<400> 305

<210> 306
<211> 53
<212> RNA
<213> Homo sapiens

<400> 306
gguggggguu ggaggcgugg guuuuagaac cuaucccuuu cuagcccuga gca   53

<210> 307
<211> 80
<212> RNA
<213> Homo sapiens

<400> 307

<210> 308
<211> 79
<212> RNA
<213> Homo sapiens

<400> 308

<210> 309
<211> 50
<212> RNA
<213> Homo sapiens

<400> 309
acccgggcgu gguggugggg gugggugccu guaauuccag cuaguuggga   50

<210> 310
<211> 88
<212> RNA
<213> Homo sapiens

<400> 310

<210> 311
<211> 62
<212> RNA
<213> Homo sapiens

<400> 311

<210> 312
<211> 73
<212> RNA
<213> Homo sapiens

<400> 312

<210> 313
<211> 65
<212> RNA
<213> Homo sapiens

<400> 313

<210> 314
<211> 73
<212> RNA
<213> Homo sapiens

<400> 314

<210> 315
<211> 93
<212> RNA
<213> Homo sapiens

<400> 315

<210> 316
<211> 87
<212> RNA
<213> Homo sapiens

<400> 316

<210> 317
<211> 51
<212> RNA
<213> Homo sapiens

<400> 317
acagaccccg gggagcccgg cggugaagcu ccugguaucc ugggugucug a   51

<210> 318
<211> 49
<212> RNA
<213> Homo sapiens

<400> 318
uucccagcca acgcaccaaa aaugauaugg gucuguuguc uggagaaac   49

<210> 319
<211> 96
<212> RNA
<213> Homo sapiens

<400> 319

<210> 320
<211> 67
<212> RNA
<213> Homo sapiens

<400> 320

<210> 321
<211> 89
<212> RNA
<213> Homo sapiens

<400> 321

<210> 322
<211> 70
<212> RNA
<213> Homo sapiens

<400> 322

<210> 323
<211> 79
<212> RNA
<213> Homo sapiens

<400> 323

<210> 324
<211> 94
<212> RNA
<213> Homo sapiens

<400> 324

<210> 325
<211> 47
<212> RNA
<213> Homo sapiens

<400> 325
cucggcgcgg ggcgcgggcu ccggguuggg gcgagccaac gccgggg   47

<210> 326
<211> 77
<212> RNA
<213> Homo sapiens

<400> 326

<210> 327
<211> 80
<212> RNA
<213> Homo sapiens

<400> 327

<210> 328
<211> 70
<212> RNA
<213> Homo sapiens

<400> 328

<210> 329
<211> 62
<212> RNA
<213> Homo sapiens

<400> 329

<210> 330
<211> 62
<212> RNA
<213> Homo sapiens

<400> 330

<210> 331
<211> 68
<212> RNA
<213> Homo sapiens

<400> 331

<210> 332
<211> 64
<212> RNA
<213> Homo sapiens

<400> 332

<210> 333
<211> 65
<212> RNA
<213> Homo sapiens

<400> 333

<210> 334
<211> 67
<212> RNA
<213> Homo sapiens

<400> 334

<210> 335
<211> 72
<212> RNA
<213> Homo sapiens

<400> 335

<210> 336
<211> 81
<212> RNA
<213> Homo sapiens

<400> 336

<210> 337
<211> 109
<212> RNA
<213> Homo sapiens

<400> 337

<210> 338
<211> 80
<212> RNA
<213> Homo sapiens

<400> 338

<210> 339
<211> 80
<212> RNA
<213> Homo sapiens

<400> 339

<210> 340
<211> 84
<212> RNA
<213> Homo sapiens

<400> 340



<210> 341
<211> 153
<212> RNA
<213> Homo sapiens

<400> 341

<210> 342
<211> 153
<212> RNA
<213> Homo sapiens

<400> 342

<210> 343
<211> 80
<212> RNA
<213> Homo sapiens

<400> 343

<210> 344
<211> 94
<212> RNA
<213> Homo sapiens

<400> 344

<210> 345
<211> 52
<212> RNA
<213> Homo sapiens

<400> 345
uagccgggcg uggugguggg ggccuguggu cccagcuacu uuggaggcug ag   52

<210> 346
<211> 70
<212> RNA
<213> Homo sapiens

<400> 346

<210> 347
<211> 83
<212> RNA
<213> Homo sapiens

<400> 347

<210> 348
<211> 90
<212> RNA
<213> Homo sapiens

<400> 348

<210> 349
<211> 85
<212> RNA
<213> Homo sapiens

<400> 349

<210> 350
<211> 89
<212> RNA
<213> Homo sapiens

<400> 350

<210> 351
<211> 70
<212> RNA
<213> Homo sapiens

<400> 351

<210> 352
<211> 66
<212> RNA
<213> Homo sapiens

<400> 352

<210> 353
<211> 62
<212> RNA
<213> Homo sapiens

<400> 353

<210> 354
<211> 97
<212> RNA
<213> Homo sapiens

<400> 354

<210> 355
<211> 85
<212> RNA
<213> Homo sapiens

<400> 355

<210> 356
<211> 83
<212> RNA
<213> Homo sapiens

<400> 356

<210> 357
<211> 93
<212> RNA
<213> Homo sapiens

<400> 357



<210> 358
<211> 90
<212> RNA
<213> Homo sapiens

<400> 358

<210> 359
<211> 74
<212> RNA
<213> Homo sapiens

<400> 359

<210> 360
<211> 73
<212> RNA
<213> Homo sapiens

<400> 360

<210> 361
<211> 70
<212> RNA
<213> Homo sapiens

<400> 361

<210> 362
<211> 65
<212> RNA
<213> Homo sapiens

<400> 362

<210> 363
<211> 84
<212> RNA
<213> Homo sapiens

<400> 363

<210> 364
<211> 86
<212> RNA
<213> Homo sapiens

<400> 364

<210> 365
<211> 75
<212> RNA
<213> Homo sapiens

<400> 365

<210> 366
<211> 68
<212> RNA
<213> Homo sapiens

<400> 366

<210> 367
<211> 64
<212> RNA
<213> Homo sapiens

<400> 367

<210> 368
<211> 64
<212> RNA
<213> Homo sapiens

<400> 368

<210> 369
<211> 110
<212> RNA
<213> Homo sapiens

<400> 369

<210> 370
<211> 67
<212> RNA
<213> Homo sapiens

<400> 370

<210> 371
<211> 67
<212> RNA
<213> Homo sapiens

<400> 371

<210> 372
<211> 89
<212> RNA
<213> Homo sapiens

<400> 372

<210> 373
<211> 66
<212> RNA
<213> Homo sapiens

<400> 373

<210> 374
<211> 90
<212> RNA
<213> Homo sapiens

<400> 374

<210> 375
<211> 63
<212> RNA
<213> Homo sapiens

<400> 375

<210> 376
<211> 78
<212> RNA
<213> Homo sapiens

<400> 376

<210> 377
<211> 90
<212> RNA
<213> Homo sapiens

<400> 377

<210> 378
<211> 54
<212> RNA
<213> Homo sapiens

<400> 378
agcagcaggg gagagagagg aguccucuag acaccgacuc ugucuccugc agau   54

<210> 379
<211> 100
<212> RNA
<213> Homo sapiens

<400> 379

<210> 380
<211> 59
<212> RNA
<213> Homo sapiens

<400> 380
guccaggcag gagccggacu ggaccucagg gaagaggcug acccggcccc ucuugcggc   59

<210> 381
<211> 54
<212> RNA
<213> Homo sapiens

<400> 381
acgcgggugc gggccggcgg gguagaagcc acccggcccg gcccggcccg gcga   54

<210> 382
<211> 73
<212> RNA
<213> Homo sapiens

<400> 382

<210> 383
<211> 69
<212> RNA
<213> Homo sapiens

<400> 383

<210> 384
<211> 69
<212> RNA
<213> Homo sapiens

<400> 384

<210> 385
<211> 70
<212> RNA
<213> Homo sapiens

<400> 385

<210> 386
<211> 72
<212> RNA
<213> Homo sapiens

<400> 386

<210> 387
<211> 67
<212> RNA
<213> Homo sapiens

<400> 387

<210> 388
<211> 94
<212> RNA
<213> Homo sapiens

<400> 388

<210> 389
<211> 88
<212> RNA
<213> Homo sapiens

<400> 389

<210> 390
<211> 94
<212> RNA
<213> Homo sapiens

<400> 390

<210> 391
<211> 94
<212> RNA
<213> Homo sapiens

<400> 391

<210> 392
<211> 59
<212> RNA
<213> Homo sapiens

<400> 392
cugugucggg gagucugggg uccggaauuc uccagagccu cugugccccu acuucccag   59

<210> 393
<211> 84
<212> RNA
<213> Homo sapiens

<400> 393

<210> 394
<211> 78
<212> RNA
<213> Homo sapiens

<400> 394

<210> 395
<211> 89
<212> RNA
<213> Homo sapiens

<400> 395

<210> 396
<211> 52
<212> RNA
<213> Homo sapiens

<400> 396
ucugggcuga gccgagcugg guuaagccga gcuggguugg gcugggcugg gu   52

<210> 397
<211> 61
<212> RNA
<213> Homo sapiens

<400> 397

<210> 398
<211> 119
<212> RNA
<213> Homo sapiens

<400> 398



<210> 399
<211> 23
<212> RNA
<213> Homo sapiens

<400> 399
cuccuggggc ccgcacucuc gcu   23

<210> 400
<211> 18
<212> RNA
<213> Homo sapiens

<400> 400
cuccuggggc ccgcacuc   18

<210> 401
<211> 22
<212> RNA
<213> Homo sapiens

<400> 401
ccgggaacgu cgagacugga gc   22

<210> 402
<211> 15
<212> RNA
<213> Homo sapiens

<400> 402
cgggaacguc gagac   15

<210> 403
<211> 22
<212> RNA
<213> Homo sapiens

<400> 403
cgcggcgggg acggcgauug gu   22

<210> 404
<211> 17
<212> RNA
<213> Homo sapiens

<400> 404
cggcggggac ggcgauu   17

<210> 405
<211> 24
<212> RNA
<213> Homo sapiens

<400> 405
gaggcuggga aggcaaaggg acgu   24

<210> 406
<211> 15
<212> RNA
<213> Homo sapiens

<400> 406
gaaggaggcu gggaa   15

<210> 407
<211> 23
<212> RNA
<213> Homo sapiens

<400> 407
ggugggugag gucgggcccc aag   23

<210> 408
<211> 20
<212> RNA
<213> Homo sapiens

<400> 408
cggggugggu gaggucgggc   20

<210> 409
<211> 17
<212> RNA
<213> Homo sapiens

<400> 409
ggugagcgcu cgcuggc   17

<210> 410
<211> 15
<212> RNA
<213> Homo sapiens

<400> 410
cggugagcgc ucgcu   15

<210> 411
<211> 26
<212> RNA
<213> Homo sapiens

<400> 411
ccuucuggag aggcuuugug cggaua   26

<210> 412
<211> 15
<212> RNA
<213> Homo sapiens

<400> 412
ccuucuggag aggcu   15

<210> 413
<211> 24
<212> RNA
<213> Homo sapiens

<400> 413
ucgaggacug guggaagggc cuuu   24

<210> 414
<211> 16
<212> RNA
<213> Homo sapiens

<400> 414
ucgaggacug guggaa   16

<210> 415
<211> 19
<212> RNA
<213> Homo sapiens

<400> 415
agugggaggc cagggcacg   19

<210> 416
<211> 15
<212> RNA
<213> Homo sapiens

<400> 416
agggggagcu gcagg   15

<210> 417
<211> 16
<212> RNA
<213> Homo sapiens

<400> 417
ugcuggugau gcuuuc   16

<210> 418
<211> 16
<212> RNA
<213> Homo sapiens

<400> 418
ugcuggugau gcuuuc   16

<210> 419
<211> 23
<212> RNA
<213> Homo sapiens

<400> 419
cggggccgua gcacugucug aga   23

<210> 420
<211> 20
<212> RNA
<213> Homo sapiens

<400> 420
cggggccgua gcacugucug   20

<210> 421
<211> 18
<212> RNA
<213> Homo sapiens

<400> 421
gaggcugaag gaagaugg   18

<210> 422
<211> 15
<212> RNA
<213> Homo sapiens

<400> 422
gaggcugaag gaaga   15

<210> 423
<211> 23
<212> RNA
<213> Homo sapiens

<400> 423
ugaggauaug gcagggaagg gga   23

<210> 424
<211> 19
<212> RNA
<213> Homo sapiens

<400> 424
ugaggauaug gcagggaag   19

<210> 425
<211> 23
<212> RNA
<213> Homo sapiens

<400> 425
agggucgggg cagggagggc agg   23

<210> 426
<211> 15
<212> RNA
<213> Homo sapiens

<400> 426
gggagaaggg ucggg   15

<210> 427
<211> 21
<212> RNA
<213> Homo sapiens

<400> 427
gaggcgaugu ggggauguag a   21

<210> 428
<211> 20
<212> RNA
<213> Homo sapiens

<400> 428
cccagucuca uuuccucauc   20

<210> 429
<211> 21
<212> RNA
<213> Homo sapiens

<400> 429
cuucccccca guaaucuuca u   21

<210> 430
<211> 21
<212> RNA
<213> Homo sapiens

<400> 430
cuucccccca guaaucuuca u   21

<210> 431
<211> 21
<212> RNA
<213> Homo sapiens

<400> 431
cccaggcugg agcgagugca g   21

<210> 432
<211> 15
<212> RNA
<213> Homo sapiens

<400> 432
agcucacugc agccu   15

<210> 433
<211> 22
<212> RNA
<213> Homo sapiens

<400> 433
caggcacggg agcucaggug ag   22

<210> 434
<211> 17
<212> RNA
<213> Homo sapiens

<400> 434
caggcacggg agcucag   17

<210> 435
<211> 16
<212> RNA
<213> Homo sapiens

<400> 435
ggacccaggg agagac   16

<210> 436
<211> 16
<212> RNA
<213> Homo sapiens

<400> 436
ggacccaggg agagac   16

<210> 437
<211> 25
<212> RNA
<213> Homo sapiens

<400> 437
uggcggcggu aguuaugggc uucuc   25

<210> 438
<211> 25
<212> RNA
<213> Homo sapiens

<400> 438
uggcggcggu aguuaugggc uucuc   25

<210> 439
<211> 21
<212> RNA
<213> Homo sapiens

<400> 439
caacucugau cucuucaucu a   21

<210> 440
<211> 20
<212> RNA
<213> Homo sapiens

<400> 440
ucucuucauc uaccccccag   20

<210> 441
<211> 23
<212> RNA
<213> Homo sapiens

<400> 441
ggcuacaaca caggacccgg gcg   23

<210> 442
<211> 21
<212> RNA
<213> Homo sapiens

<400> 442
ggcuacaaca caggacccgg g   21

<210> 443
<211> 23
<212> RNA
<213> Homo sapiens

<400> 443
agaagaaggc ggucggucug cgg   23

<210> 444
<211> 21
<212> RNA
<213> Homo sapiens

<400> 444
aagaaggcgg ucggucugcg g   21

<210> 445
<211> 20
<212> RNA
<213> Homo sapiens

<400> 445
aagacacauu uggagaggga   20

<210> 446
<211> 16
<212> RNA
<213> Homo sapiens

<400> 446
agacacauuu ggagag   16

<210> 447
<211> 26
<212> RNA
<213> Homo sapiens

<400> 447
aggagggagg agaugggcca aguucc   26

<210> 448
<211> 15
<212> RNA
<213> Homo sapiens

<400> 448
gggaggaggg aggag   15

<210> 449
<211> 25
<212> RNA
<213> Homo sapiens

<400> 449
ugcggggcua gggcuaacag caguc   25

<210> 450
<211> 15
<212> RNA
<213> Homo sapiens

<400> 450
ugcggggcua gggcu   15

<210> 451
<211> 20
<212> RNA
<213> Homo sapiens

<400> 451
cuccccggug ugcaaaugug   20

<210> 452
<211> 15
<212> RNA
<213> Homo sapiens

<400> 452
gugugcggug uuaug   15

<210> 453
<211> 22
<212> RNA
<213> Homo sapiens

<400> 453
ccucacaccu gccucgcccc cc   22

<210> 454
<211> 15
<212> RNA
<213> Homo sapiens

<400> 454
ucacaccugc cucgc   15

<210> 455
<211> 24
<212> RNA
<213> Homo sapiens

<400> 455
uggggagcug aggcucuggg ggug   24

<210> 456
<211> 15
<212> RNA
<213> Homo sapiens

<400> 456
ggcccugggg agcug   15

<210> 457
<211> 27
<212> RNA
<213> Homo sapiens

<400> 457
gugaacgggc gccaucccga ggcuuug   27

<210> 458
<211> 16
<212> RNA
<213> Homo sapiens

<400> 458
gugaacgggc gccauc   16

<210> 459
<211> 21
<212> RNA
<213> Homo sapiens

<400> 459
gagggcagcg uggguguggc g   21

<210> 460
<211> 21
<212> RNA
<213> Homo sapiens

<400> 460
gagggcagcg uggguguggc g   21

<210> 461
<211> 23
<212> RNA
<213> Homo sapiens

<400> 461
gggggucccc ggugcucgga ucu   23

<210> 462
<211> 16
<212> RNA
<213> Homo sapiens

<400> 462
ucgggagggg cgggag   16

<210> 463
<211> 25
<212> RNA
<213> Homo sapiens

<400> 463
uucugggccc gcggcgggcg ugggg   25

<210> 464
<211> 15
<212> RNA
<213> Homo sapiens

<400> 464
cgcggcgggc guggg   15

<210> 465
<211> 22
<212> RNA
<213> Homo sapiens

<400> 465
ugggagggga gaggcagcaa gc   22

<210> 466
<211> 22
<212> RNA
<213> Homo sapiens

<400> 466
ugggagggga gaggcagcaa gc   22

<210> 467
<211> 21
<212> RNA
<213> Homo sapiens

<400> 467
aggaggcagu gggcgagcag g   21

<210> 468
<211> 21
<212> RNA
<213> Homo sapiens

<400> 468
aggaggcagu gggcgagcag g   21

<210> 469
<211> 15
<212> RNA
<213> Homo sapiens

<400> 469
ugaagcgggg gggcg   15

<210> 470
<211> 15
<212> RNA
<213> Homo sapiens

<400> 470
ugaagcgggg gggcg   15

<210> 471
<211> 17
<212> RNA
<213> Homo sapiens

<400> 471
uccuagucac ggcacca   17

<210> 472
<211> 17
<212> RNA
<213> Homo sapiens

<400> 472
uccuagucac ggcacca   17

<210> 473
<211> 23
<212> RNA
<213> Homo sapiens

<400> 473
ggaggcgcag gcucggaaag gcg   23

<210> 474
<211> 15
<212> RNA
<213> Homo sapiens

<400> 474
gcaggcucgg aaagg   15

<210> 475
<211> 23
<212> RNA
<213> Homo sapiens

<400> 475
cuaguggaag aagauggcgg aag   23

<210> 476
<211> 15
<212> RNA
<213> Homo sapiens

<400> 476
uaguggaaga agaug   15

<210> 477
<211> 23
<212> RNA
<213> Homo sapiens

<400> 477
acaggagugg gggugggaca uaa   23

<210> 478
<211> 20
<212> RNA
<213> Homo sapiens

<400> 478
acaggagugg gggugggaca   20

<210> 479
<211> 25
<212> RNA
<213> Homo sapiens

<400> 479
agcggggagg aagugggcgc ugcuu   25

<210> 480
<211> 21
<212> RNA
<213> Homo sapiens

<400> 480
agcggggagg aagugggcgc u   21

<210> 481
<211> 22
<212> RNA
<213> Homo sapiens

<400> 481
ccggcagagg aggcugcaga gg   22

<210> 482
<211> 19
<212> RNA
<213> Homo sapiens

<400> 482
ccggcagagg aggcugcag   19

<210> 483
<211> 15
<212> RNA
<213> Homo sapiens

<400> 483
ucugggcgag gggug   15

<210> 484
<211> 15
<212> RNA
<213> Homo sapiens

<400> 484
ucugggcgag gggug   15

<210> 485
<211> 26
<212> RNA
<213> Homo sapiens

<400> 485
gucccggggc ugcgcgaggc acaggc   26

<210> 486
<211> 15
<212> RNA
<213> Homo sapiens

<400> 486
ggcccggggg gcggg   15

<210> 487
<211> 21
<212> RNA
<213> Homo sapiens

<400> 487
cggauccgag ucacggcacc a   21

<210> 488
<211> 15
<212> RNA
<213> Homo sapiens

<400> 488
ggauccgagu cacgg   15

<210> 489
<211> 21
<212> RNA
<213> Homo sapiens

<400> 489
auccaguucu cugagggggc u   21

<210> 490
<211> 21
<212> RNA
<213> Homo sapiens

<400> 490
auccaguucu cugagggggc u   21

<210> 491
<211> 23
<212> RNA
<213> Homo sapiens

<400> 491
ggcccggccg ugccugaggu uuc   23

<210> 492
<211> 15
<212> RNA
<213> Homo sapiens

<400> 492
ggcgguggga ucccg   15

<210> 493
<211> 18
<212> RNA
<213> Homo sapiens

<400> 493
ucuagguggg gagacuga   18

<210> 494
<211> 16
<212> RNA
<213> Homo sapiens

<400> 494
guggggagac ugacgg   16

<210> 495
<211> 17
<212> RNA
<213> Homo sapiens

<400> 495
ugcaggggca ggccagc   17

<210> 496
<211> 17
<212> RNA
<213> Homo sapiens

<400> 496
ugcaggggca ggccagc   17

<210> 497
<211> 25
<212> RNA
<213> Homo sapiens

<400> 497
aaggcagggc ccccgcuccc cgggc   25

<210> 498
<211> 15
<212> RNA
<213> Homo sapiens

<400> 498
guguguugag gaagg   15

<210> 499
<211> 26
<212> RNA
<213> Homo sapiens

<400> 499
gcgggcuguc cggagggguc ggcuuu   26

<210> 500
<211> 16
<212> RNA
<213> Homo sapiens

<400> 500
gcuguccgga gggguc   16

<210> 501
<211> 20
<212> RNA
<213> Homo sapiens

<400> 501
ggcuggucag augggagugg   20

<210> 502
<211> 20
<212> RNA
<213> Homo sapiens

<400> 502
ggcuggucag augggagugg   20

<210> 503
<211> 24
<212> RNA
<213> Homo sapiens

<400> 503
cugguacagg ccugggggac aggg   24

<210> 504
<211> 18
<212> RNA
<213> Homo sapiens

<400> 504
cugguacagg ccuggggg   18

<210> 505
<211> 23
<212> RNA
<213> Homo sapiens

<400> 505
gccccggcgc gggcggguuc ugg   23

<210> 506
<211> 16
<212> RNA
<213> Homo sapiens

<400> 506
ggagccccgg cgcggg   16

<210> 507
<211> 20
<212> RNA
<213> Homo sapiens

<400> 507
ccccagggcg acgcggcggg   20

<210> 508
<211> 15
<212> RNA
<213> Homo sapiens

<400> 508
cgcggcgggg gcggc   15

<210> 509
<211> 21
<212> RNA
<213> Homo sapiens

<400> 509
gugagucagg guggggcugg c   21

<210> 510
<211> 21
<212> RNA
<213> Homo sapiens

<400> 510
gugagucagg guggggcugg c   21

<210> 511
<211> 21
<212> RNA
<213> Homo sapiens

<400> 511
guuggaggcg uggguuuuag a   21

<210> 512
<211> 15
<212> RNA
<213> Homo sapiens

<400> 512
guuggaggcg ugggu   15

<210> 513
<211> 23
<212> RNA
<213> Homo sapiens

<400> 513
aggagggguc ccgcacuggg agg   23

<210> 514
<211> 15
<212> RNA
<213> Homo sapiens

<400> 514
ugggaggggc ccuca   15

<210> 515
<211> 23
<212> RNA
<213> Homo sapiens

<400> 515
gugggcuggg cugggcuggg cca   23

<210> 516
<211> 15
<212> RNA
<213> Homo sapiens

<400> 516
gggcugggcu gggcu   15

<210> 517
<211> 24
<212> RNA
<213> Homo sapiens

<400> 517
cgggcguggu ggugggggug ggug   24

<210> 518
<211> 15
<212> RNA
<213> Homo sapiens

<400> 518
cgggcguggu ggugg   15

<210> 519
<211> 18
<212> RNA
<213> Homo sapiens

<400> 519
ggugggcuuc ccggaggg   18

<210> 520
<211> 15
<212> RNA
<213> Homo sapiens

<400> 520
ggugggcuuc ccgga   15

<210> 521
<211> 26
<212> RNA
<213> Homo sapiens

<400> 521
cggugggauc ccgcggccgu guuuuc   26

<210> 522
<211> 15
<212> RNA
<213> Homo sapiens

<400> 522
ggggcgccgc gggac   15

<210> 523
<211> 25
<212> RNA
<213> Homo sapiens

<400> 523
ugggcagggg cuuauuguag gaguc   25

<210> 524
<211> 19
<212> RNA
<213> Homo sapiens

<400> 524
ugggcagggg cuuauugua   19

<210> 525
<211> 20
<212> RNA
<213> Homo sapiens

<400> 525
ccccggggag cccggcggug   20

<210> 526
<211> 15
<212> RNA
<213> Homo sapiens

<400> 526
accccgggga gcccg   15

<210> 527
<211> 26
<212> RNA
<213> Homo sapiens

<400> 527
agggacggga cgcggugcag uguugu   26

<210> 528
<211> 15
<212> RNA
<213> Homo sapiens

<400> 528
ggcgggcggg aggga   15

<210> 529
<211> 22
<212> RNA
<213> Homo sapiens

<400> 529
acucaaacug ugggggcacu uu   22

<210> 530
<211> 19
<212> RNA
<213> Homo sapiens

<400> 530
acucaaacug ugggggcac   19

<210> 531
<211> 16
<212> RNA
<213> Homo sapiens

<400> 531
gugaaggccc ggcgga   16

<210> 532
<211> 15
<212> RNA
<213> Homo sapiens

<400> 532
gugaaggccc ggcgg   15

<210> 533
<211> 24
<212> RNA
<213> Homo sapiens

<400> 533
gcugcgggcu gcggucaggg cgau   24

<210> 534
<211> 20
<212> RNA
<213> Homo sapiens

<400> 534
gcugcgggcu gcggucaggg   20

<210> 535
<211> 30
<212> RNA
<213> Homo sapiens

<400> 535
ugaggggcag agagcgagac uuuucuauuu   30

<210> 536
<211> 15
<212> RNA
<213> Homo sapiens

<400> 536
ugaggggcag agagc   15

<210> 537
<211> 23
<212> RNA
<213> Homo sapiens

<400> 537
caccuugccu ugcugcccgg gcc   23

<210> 538
<211> 22
<212> RNA
<213> Homo sapiens

<400> 538
caccuugccu ugcugcccgg gc   22

<210> 539
<211> 21
<212> RNA
<213> Homo sapiens

<400> 539
ugggaauggg gguaagggcc u   21

<210> 540
<211> 15
<212> RNA
<213> Homo sapiens

<400> 540
cuucugagcc caggu   15

<210> 541
<211> 15
<212> RNA
<213> Homo sapiens

<400> 541
ggcggcgggc ccggg   15

<210> 542
<211> 15
<212> RNA
<213> Homo sapiens

<400> 542
ggcggcgggc ccggg   15

<210> 543
<211> 16
<212> RNA
<213> Homo sapiens

<400> 543
cugggggucc cccgac   16

<210> 544
<211> 15
<212> RNA
<213> Homo sapiens

<400> 544
guguggagcu ggggc   15

<210> 545
<211> 22
<212> RNA
<213> Homo sapiens

<400> 545
ugugggacug caaaugggag cu   22

<210> 546
<211> 22
<212> RNA
<213> Homo sapiens

<400> 546
ugugggacug caaaugggag cu   22

<210> 547
<211> 23
<212> RNA
<213> Homo sapiens

<400> 547
acagcagggc uggggauugc agu   23

<210> 548
<211> 19
<212> RNA
<213> Homo sapiens

<400> 548
ugcugcuccc aguccugcc   19

<210> 549
<211> 17
<212> RNA
<213> Homo sapiens

<400> 549
aggggcuggg cgcgcgc   17

<210> 550
<211> 15
<212> RNA
<213> Homo sapiens

<400> 550
caggggcugg gcgcg   15

<210> 551
<211> 17
<212> RNA
<213> Homo sapiens

<400> 551
ggggcggggg cgggggc   17

<210> 552
<211> 15
<212> RNA
<213> Homo sapiens

<400> 552
cgcgccgggc ccggg   15

<210> 553
<211> 23
<212> RNA
<213> Homo sapiens

<400> 553
uggggcggag cuuccggagg ccc   23

<210> 554
<211> 16
<212> RNA
<213> Homo sapiens

<400> 554
aucgcuggcc uggucg   16

<210> 555
<211> 22
<212> RNA
<213> Homo sapiens

<400> 555
gaggguuggg uggaggcucu cc   22

<210> 556
<211> 15
<212> RNA
<213> Homo sapiens

<400> 556
gaggguuggg uggag   15

<210> 557
<211> 18
<212> RNA
<213> Homo sapiens

<400> 557
cuccgggcgg cgccgugu   18

<210> 558
<211> 18
<212> RNA
<213> Homo sapiens

<400> 558
cuccgggcgg cgccgugu   18

<210> 559
<211> 21
<212> RNA
<213> Homo sapiens

<400> 559
gccgggcgug gugguggggg c   21

<210> 560
<211> 15
<212> RNA
<213> Homo sapiens

<400> 560
uagccgggcg uggug   15

<210> 561
<211> 16
<212> RNA
<213> Homo sapiens

<400> 561
ggcggugggc ggcggg   16

<210> 562
<211> 15
<212> RNA
<213> Homo sapiens

<400> 562
ggccucucgg gaacu   15

<210> 563
<211> 20
<212> RNA
<213> Homo sapiens

<400> 563
aucccaccac ugccaccauu   20

<210> 564
<211> 15
<212> RNA
<213> Homo sapiens

<400> 564
aucccaccac ugcca   15

<210> 565
<211> 25
<212> RNA
<213> Homo sapiens

<400> 565
caggaaggau uuagggacag gcuuu   25

<210> 566
<211> 19
<212> RNA
<213> Homo sapiens

<400> 566
caggaaggau uuagggaca 19

<210> 567
<211> 26
<212> RNA
<213> Homo sapiens

<400> 567
aaaaucacau ugccagggau uaccac   26

<210> 568
<211> 15
<212> RNA
<213> Homo sapiens

<400> 568
aaucacauug ccagg   15

<210> 569
<211> 23
<212> RNA
<213> Homo sapiens

<400> 569
uaggggcagc agaggaccug ggc   23

<210> 570
<211> 20
<212> RNA
<213> Homo sapiens

<400> 570
uaggggcagc agaggaccug   20

<210> 571
<211> 22
<212> RNA
<213> Homo sapiens

<400> 571
accccacucc ugguaccaua gu   22

<210> 572
<211> 15
<212> RNA
<213> Homo sapiens

<400> 572
accccacucc uggua   15

<210> 573
<211> 25
<212> RNA
<213> Homo sapiens

<400> 573
cugggccagg gagcagcugg ugggu   25

<210> 574
<211> 20
<212> RNA
<213> Homo sapiens

<400> 574
ugggccaggg agcagcuggu   20

<210> 575
<211> 23
<212> RNA
<213> Homo sapiens

<400> 575
aagggaggag gagcggaggg gcc   23

<210> 576
<211> 15
<212> RNA
<213> Homo sapiens

<400> 576
gggaggagga gcgga   15

<210> 577
<211> 20
<212> RNA
<213> Homo sapiens

<400> 577
aucccaccuc ugccaccaaa   20

<210> 578
<211> 15
<212> RNA
<213> Homo sapiens

<400> 578
aucccaccuc ugcca   15

<210> 579
<211> 23
<212> RNA
<213> Homo sapiens

<400> 579
gggggccgau acacuguacg aga   23

<210> 580
<211> 20
<212> RNA
<213> Homo sapiens

<400> 580
gggggccgau acacuguacg   20

<210> 581
<211> 23
<212> RNA
<213> Homo sapiens

<400> 581
cacaggugag guucuuggga gcc   23

<210> 582
<211> 15
<212> RNA
<213> Homo sapiens

<400> 582
acaggugagg uucuu   15

<210> 583
<211> 25
<212> RNA
<213> Homo sapiens

<400> 583
ggguggggau uuguugcauu acuug   25

<210> 584
<211> 20
<212> RNA
<213> Homo sapiens

<400> 584
ggguggggau uuguugcauu   20

<210> 585
<211> 23
<212> RNA
<213> Homo sapiens

<400> 585
cggggcagcu caguacagga uac   23

<210> 586
<211> 15
<212> RNA
<213> Homo sapiens

<400> 586
agcucaguac aggau   15

<210> 587
<211> 17
<212> RNA
<213> Homo sapiens

<400> 587
gcggggcggc aggggcc   17

<210> 588
<211> 15
<212> RNA
<213> Homo sapiens

<400> 588
gggggcgggg cggca   15

<210> 589
<211> 22
<212> RNA
<213> Homo sapiens

<400> 589
ggcagggaca gcaaaggggu gc   22

<210> 590
<211> 18
<212> RNA
<213> Homo sapiens

<400> 590
gcagggacag caaagggg   18

<210> 591
<211> 16
<212> RNA
<213> Homo sapiens

<400> 591
ugggggggaa gaaaag   16

<210> 592
<211> 16
<212> RNA
<213> Homo sapiens

<400> 592
ugggggggaa gaaaag   16

<210> 593
<211> 23
<212> RNA
<213> Homo sapiens

<400> 593
gagggaggga cgggggcugu gcu   23

<210> 594
<211> 15
<212> RNA
<213> Homo sapiens

<400> 594
gaggagggag ggagg   15

<210> 595
<211> 24
<212> RNA
<213> Homo sapiens

<400> 595
ugacugggga gcagaaggag aacc   24

<210> 596
<211> 15
<212> RNA
<213> Homo sapiens

<400> 596
gacuggggag cagaa   15

<210> 597
<211> 22
<212> RNA
<213> Homo sapiens

<400> 597
auauagggau uggagccgug gc   22

<210> 598
<211> 20
<212> RNA
<213> Homo sapiens

<400> 598
auauagggau uggagccgug   20

<210> 599
<211> 19
<212> RNA
<213> Homo sapiens

<400> 599
gcugggcgag gcuggcauc   19

<210> 600
<211> 17
<212> RNA
<213> Homo sapiens

<400> 600
gcugggcgag gcuggca   17

<210> 601
<211> 23
<212> RNA
<213> Homo sapiens

<400> 601
uggggaaggc gucagugucg ggu   23

<210> 602
<211> 16
<212> RNA
<213> Homo sapiens

<400> 602
uggggaaggc gucagu   16

<210> 603
<211> 21
<212> RNA
<213> Homo sapiens

<400> 603
cagcagggga gagagaggag u   21

<210> 604
<211> 20
<212> RNA
<213> Homo sapiens

<400> 604
cagcagggga gagagaggag   20

<210> 605
<211> 26
<212> RNA
<213> Homo sapiens

<400> 605
agggcuggac ucagcggcgg agcugg   26

<210> 606
<211> 17
<212> RNA
<213> Homo sapiens

<400> 606
gcggcggagc uggcugc   17

<210> 607
<211> 24
<212> RNA
<213> Homo sapiens

<400> 607
caggcaggag ccggacugga ccuc   24

<210> 608
<211> 21
<212> RNA
<213> Homo sapiens

<400> 608
uccaggcagg agccggacug g   21

<210> 609
<211> 19
<212> RNA
<213> Homo sapiens

<400> 609
gggugcgggc cggcggggu   19

<210> 610
<211> 15
<212> RNA
<213> Homo sapiens

<400> 610
ugcgggccgg cgggg   15

<210> 611
<211> 27
<212> RNA
<213> Homo sapiens

<400> 611
aucacauugc cagggauuuc caaccga   27

<210> 612
<211> 15
<212> RNA
<213> Homo sapiens

<400> 612
aaucacauug ccagg   15

<210> 613
<211> 19
<212> RNA
<213> Homo sapiens

<400> 613
uggcgggugc ggggguggg   19

<210> 614
<211> 15
<212> RNA
<213> Homo sapiens

<400> 614
uggcgggugc ggggg   15

<210> 615
<211> 21
<212> RNA
<213> Homo sapiens

<400> 615
uugaggagac augguggggg c   21

<210> 616
<211> 15
<212> RNA
<213> Homo sapiens

<400> 616
uugaggagac auggu   15

<210> 617
<211> 27
<212> RNA
<213> Homo sapiens

<400> 617
aaaccguuac cauuacugag uuuagua   27

<210> 618
<211> 15
<212> RNA
<213> Homo sapiens

<400> 618
gaaaccguua ccauu   15

<210> 619
<211> 23
<212> RNA
<213> Homo sapiens

<400> 619
ccagggcugg cagugacaug ggu   23

<210> 620
<211> 19
<212> RNA
<213> Homo sapiens

<400> 620
cagggcuggc agugacaug   19

<210> 621
<211> 23
<212> RNA
<213> Homo sapiens

<400> 621
uggggcggag cuuccggagg ccc   23

<210> 622
<211> 15
<212> RNA
<213> Homo sapiens

<400> 622
gccccgggaa agcgu   15

<210> 623
<211> 24
<212> RNA
<213> Homo sapiens

<400> 623
agacacauuu ggagagggaa ccuc   24

<210> 624
<211> 16
<212> RNA
<213> Homo sapiens

<400> 624
agacacauuu ggagag   16

<210> 625
<211> 24
<212> RNA
<213> Homo sapiens

<400> 625
gaucggucga gagcguccug gcug   24

<210> 626
<211> 15
<212> RNA
<213> Homo sapiens

<400> 626
gcugggcggg gcgcg   15

<210> 627
<211> 23
<212> RNA
<213> Homo sapiens

<400> 627
cugggggacg cgugagcgcg agc   23

<210> 628
<211> 21
<212> RNA
<213> Homo sapiens

<400> 628
cugggggacg cgugagcgcg a   21

<210> 629
<211> 27
<212> RNA
<213> Homo sapiens

<400> 629
caagguggcu gggagagggu uguuuac   27

<210> 630
<211> 15
<212> RNA
<213> Homo sapiens

<400> 630
gugagcucaa ggugg   15

<210> 631
<211> 29
<212> RNA
<213> Homo sapiens

<400> 631
gcuggguuaa gccgagcugg guugggcug   29

<210> 632
<211> 19
<212> RNA
<213> Homo sapiens

<400> 632
cuggguuggg cugggcugg   19

<210> 633
<211> 19
<212> RNA
<213> Homo sapiens

<400> 633
gagggcgggu ggaggagga   19

<210> 634
<211> 15
<212> RNA
<213> Homo sapiens

<400> 634
gcggguggag gagga   15

<210> 635
<211> 20
<212> RNA
<213> Homo sapiens

<400> 635
cagggggacu gggggugagc   20

<210> 636
<211> 25
<212> RNA
<213> Homo sapiens

<400> 636
acuugggcag gagggacccu guaug   25

<210> 637
<211> 22
<212> RNA
<213> Homo sapiens

<400> 637
agcccgcccc agccgagguu cu   22

<210> 638
<211> 17
<212> RNA
<213> Homo sapiens

<400> 638
ggauggagga ggggucu   17

<210> 639
<211> 17
<212> RNA
<213> Homo sapiens

<400> 639
gggagucuac agcaggg   17

<210> 640
<211> 22
<212> RNA
<213> Homo sapiens

<400> 640
gugcggaacg cuggccgggg cg   22

<210> 641
<211> 24
<212> RNA
<213> Homo sapiens

<400> 641
ggaggccggg guggggeggg gcgg   24

<210> 642
<211> 23
<212> RNA
<213> Homo sapiens

<400> 642
aggaagcccu ggaggggcug gag   23

<210> 643
<211> 68
<212> RNA
<213> Homo sapiens

<400> 643

<210> 644
<211> 70
<212> RNA
<213> Homo sapiens

<400> 644

<210> 645
<211> 80
<212> RNA
<213> Homo sapiens

<400> 645

<210> 646
<211> 60
<212> RNA
<213> Homo sapiens

<400> 646
ugugaaugac ccccuuccag agccaaaauc accagggaug gaggaggggu cuuggguacu   60

<210> 647
<211> 76
<212> RNA
<213> Homo sapiens

<400> 647

<210> 648
<211> 61
<212> RNA
<213> Homo sapiens

<400> 648

<210> 649
<211> 64
<212> RNA
<213> Homo sapiens

<400> 649

<210> 650
<211> 64
<212> RNA
<213> Homo sapiens

<400> 650

<210> 651
<211> 118
<212> RNA
<213> Homo sapiens

<400> 651

<210> 652
<211> 23
<212> RNA
<213> Homo sapiens

<400> 652
cagcccgccc cagccgaggu ucu   23

<210> 653
<211> 17
<212> RNA
<213> Homo sapiens

<400> 653
agcccgcccc agccgag   17

<210> 654
<211> 16
<212> RNA
<213> Homo sapiens

<400> 654
cgggcccggc guuccc   16

<210> 655
<211> 15
<212> RNA
<213> Homo sapiens

<400> 655
ccgggcccgg cguuc   15

<210> 656
<211> 25
<212> RNA
<213> Homo sapiens

<400> 656
aggaagcccu ggaggggcug gaggu   25

<210> 657
<211> 15
<212> RNA
<213> Homo sapiens

<400> 657
aggaagagga ggaag   15




Claims

1. Use of a stomach cancer marker polynucleotide miR-4257 in an in vitro method of detection or diagnosis of stomach cancer.
 
2. Use according to claim 1, wherein miR-4257 is used together with at least one or more polynucleotide(s) selected from the group consisting of stomach cancer markers: miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 and miR-671-5p, and/or;
at least one or more polynucleotide(s) selected from the group consisting of other stomach cancer markers miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, miR-486-3p, miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 and miR-1199-5p.
 
3. Use according to claim 1 or claim 2, which is the use of a kit comprising a nucleic acid(s) capable of specifically binding to a polynucleotide of stomach cancer marker miR-4257.
 
4. Use according to claim 3, wherein the nucleic acid is a polynucleotide selected from the group consisting of the following polynucleotides (a) to (e):

(a) a polynucleotide consisting of a nucleotide sequence represented by SEQ ID NO: 1 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(b) a polynucleotide comprising a nucleotide sequence represented by SEQ ID NO: 1,

(c) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by SEQ ID NO: 1 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(d) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by SEQ ID NO: 1 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, and

(e) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a) to (d).


 
5. Use according to claim 3 or 4, wherein the kit further comprises a nucleic acid(s) capable of specifically binding to at least one or more polynucleotides selected from the group consisting of the following other stomach cancer markers: miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 and miR-671-5p, and/or; miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, miR-486-3p, miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 and miR-1199-5p.
 
6. Use according to claim 5, wherein the nucleic acid is a polynucleotide selected from the group consisting of the following polynucleotides (a') to (e'):

(a') a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 2 to 165 and 635 to 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(b') a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 2 to 165 and 635 to 642,

(c') a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by SEQ ID NOs: 2 to 165 and 635 to 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(d') a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 2 to 165 and 635 to 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, and

(e') a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a) to (d'), and/or;
a polynucleotide selected from the group consisting of the following polynucleotides (f) to (o): (f) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(g) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169,

(h) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(i) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t,

(j) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (f) to (i),

(k) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(1) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199,

(m) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(n) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, and

(o) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (k) to (n).


 
7. Use according to any one of claims 3 to 6, wherein the kit comprises at least two or more nucleic acids capable of specifically binding to at least two or more polynucleotides, respectively, selected from all of the stomach cancer markers according to claim 5.
 
8. Use according to claim 1 or claim 2, which is the use of a device comprising a nucleic acid(s) capable of specifically binding to a polynucleotide of stomach cancer marker: miR-4257.
 
9. Use according to claim 8, wherein the nucleic acid is a polynucleotide selected from the group consisting of the following polynucleotides (a) to (e):

(a) a polynucleotide consisting of a nucleotide sequence represented by SEQ ID NO: 1 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(b) a polynucleotide comprising a nucleotide sequence represented by SEQ ID NO: 1,

(c) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by SEQ ID NO: 1 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(d) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by SEQ ID NO: 1 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, and

(e) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a) to (d).


 
10. Use according to claim 8 or 9, wherein the device further comprises a nucleic acid(s) capable of specifically binding to at least one or more polynucleotides selected from the group consisting of following other stomach cancer markers: miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 and miR-671-5p, and/or;
miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, miR-486-3p, miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 and miR-1199-5p.
 
11. Use according to claim 10, wherein the nucleic acid is a polynucleotide selected from the group consisting of the following polynucleotides (a') to (e'):

(a') a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 2 to 165 and 635 to 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(b') a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 2 to 165 and 635 to 642,

(c') a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by SEQ ID NOs 2 to 165 and 635 to 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(d') a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 2 to 165 and 635 to 642 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, and

(e') a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a) to (d'), and/or; a polynucleotide selected from the group consisting of the following polynucleotides (f) to (o):

(f) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(g) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169,

(h) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(i) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 166 to 169 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t,

(j) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (f) to (i),

(k) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(l) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199,

(m) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides,

(n) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 170 to 199 or a nucleotide sequence derived from the nucleotide sequence by the replacement of u with t, and

(o) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (k) to (n).


 
12. Use according to any one of claims 8 to 11, wherein the device is a device for measurement by a hybridization technique.
 
13. Use according to claim 12, wherein the hybridization technique is a nucleic acid array technique.
 
14. Use according to any one of claims 8 to 13, wherein the device comprises at least two or more nucleic acids capable of specifically binding to at least two or more polynucleotides, respectively, selected from all of the stomach cancer markers according to claim 10.
 
15. A method for detecting stomach cancer, comprising measuring an expression level(s) of a target nucleic acid(s) in a sample from a subject using the kit defined in any one of claims 3 to 7 or the device defined in any one of claims 8 14, and evaluating in vitro whether or not the subject has stomach cancer using both of the measured expression level(s) and control expression level(s) in a sample from a healthy subject measured in the same way, wherein the target nucleic acid(s) comprise stomach cancer marker polynucleotide miR-4257.
 
16. The method according to claim 15, wherein the target nucleic acid(s) further comprise at least one or more polynucleotide(s) selected from the group consisting of stomach cancer markers: miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 and miR-671-5p, and/or;
at least one or more polynucleotide(s) selected from the group consisting of other stomach cancer markers miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, miR-486-3p, miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 and miR-1199-5p.
 
17. The method according to claim 15 or claim 16, wherein the subject is a human.
 
18. The method according to any one of claims 15 to 17, wherein the sample is blood, serum, or plasma.
 


Ansprüche

1. Verwendung eines Magenkrebsmarker-Polynucleotids miR-4257 in einem In-vitro-Verfahren zur Detektion oder Diagnose von Magenkrebs.
 
2. Verwendung nach Anspruch 1, wobei miR-4257 zusammen mit zumindest einem oder mehreren Polynucleotiden verwendet wird, das/die aus der aus folgenden Magenkrebsmarkern bestehenden Gruppe ausgewählt ist/sind: miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 und miR-671-5p; und/oder
zumindest einem oder mehreren Polynucleotiden, das/die aus folgender aus weiteren Magenkrebsmarkern bestehenden Gruppe ausgewählt ist/sind:
miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, miR-486-3p, miR-3196, miR-211 - 3p, miR-4271, miR-6851-5p. miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 und miR-1199-5p.
 
3. Verwendung nach Anspruch 1 oder 2, wobei es sich um die Verwendung eines Sets handelt, das eine Nucleinsäure/Nucleinsäuren umfasst, die in der Lage ist/sind, spezifisch an ein Polynucleotid des Magenkrebsmarkers miR-4257 zu binden.
 
4. Verwendung nach Anspruch 3, wobei die Nucleinsäure ein Polynucleotid ist, das aus der aus folgenden Polynucleotiden (a) bis (e) bestehenden Gruppe ausgewählt ist:

(a) einem Polynucleotid, das aus einer Nucleotidsequenz mit SEQ ID No. 1 oder einer von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz besteht, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(b) einem Polynucleotid, das eine Nucleotidsequenz mit SEQ ID No. 1 umfasst;

(c) einem Polynucleotid, das aus einer Nucleotidsequenz besteht, die in Bezug auf eine Nucleotidsequenz mit SEQ ID No. 1 oder eine von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz komplementär ist, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(d) einem Polynucleotid, das eine Nucleotidsequenz umfasst, die in Bezug auf eine Nucleotidsequenz mit SEQ ID No. 1 oder eine von der Nucleotidsequenz durch das Ersetzen von u durch t abgeleitete Nucleotidsequenz komplementär ist, und

(e) einem Polynucleotid, das unter stringenten Bedingungen an ein beliebiges der Polynucleotide (a) bis (d) hybridisiert.


 
5. Verwendung nach Anspruch 3 oder 4, wobei das Set außerdem eine Nucleinsäure/Nucleinsäuren umfasst, die in der Lage ist/sind, spezifisch an zumindest ein oder mehrere Polynucleotide zu binden, die aus der aus folgenden weiteren Magenkrebsmarkern bestehenden Gruppe ausgewählt sind: miR-6726-5p, miR-1343-3p, miR-1247-3p,
miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-71 10-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 und miR-671-5p und/oder miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, miR-486-3p, miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 und miR-1199-5p.
 
6. Verwendung nach Anspruch 5, wobei die Nucleinsäure ein Polynucleotid ist, das aus der aus folgenden Polynucleotiden (a') bis (e') bestehenden Gruppe ausgewählt ist:

(a') einem Polynucleotid, das aus einer Nucleotidsequenz mit einer beliebigen der SEQ ID No. 2 bis 165 und 635 bis 642 oder einer von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz besteht, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(b') einem Polynucleotid, das eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 2 bis 165 und 635 bis 642 umfasst;

(c') einem Polynucleotid, das aus einer Nucleotidsequenz besteht, die in Bezug auf eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 2 bis 165 und 635 bis 642 oder eine von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz komplementär ist, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(d') einem Polynucleotid, das eine Nucleotidsequenz umfasst, die in Bezug auf eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 2 bis 165 und 635 bis 642 oder eine von der Nucleotidsequenz durch das Ersetzen von u durch t abgeleitete Nucleotidsequenz komplementär ist, und

(e') einem Polynucleotid, das unter stringenten Bedingungen an ein beliebiges der Polynucleotide (a') bis (d') hybridisiert; und/oder

ein Polynucleotid ist, das aus der aus folgenden Polynucleotiden (f) bis (o) bestehenden Gruppe ausgewählt ist:

(f) einem Polynucleotid, das aus einer Nucleotidsequenz mit einer beliebigen der SEQ ID No. 166 bis 169 oder einer von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz besteht, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(g) einem Polynucleotid, das eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 166 bis 169 umfasst;

(h) einem Polynucleotid, das aus einer Nucleotidsequenz besteht, die in Bezug auf eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 166 bis 169 oder eine von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz komplementär ist, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(i) einem Polynucleotid, das eine Nucleotidsequenz umfasst, die in Bezug auf eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 166 bis 169 oder eine von der Nucleotidsequenz durch das Ersetzen von u durch t abgeleitete Nucleotidsequenz komplementär ist, und

(j) einem Polynucleotid, das unter stringenten Bedingungen an ein beliebiges der Polynucleotide (f) bis (i) hybridisiert;

(k) einem Polynucleotid, das aus einer Nucleotidsequenz mit einer beliebigen der SEQ ID No. 170 bis 199 oder einer von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz besteht, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(l) einem Polynucleotid, das eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 170 bis 199 umfasst;

(m) einem Polynucleotid, das aus einer Nucleotidsequenz besteht, die in Bezug auf eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 170 bis 199 oder eine von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz komplementär ist, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(n) einem Polynucleotid, das eine Nucleotidsequenz umfasst, die in Bezug auf eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 170 bis 199 oder eine von der Nucleotidsequenz durch das Ersetzen von u durch t abgeleitete Nucleotidsequenz komplementär ist, und

(o) einem Polynucleotid, das unter stringenten Bedingungen an ein beliebiges der Polynucleotide (k) bis (n) hybridisiert.


 
7. Verwendung nach einem der Ansprüche 3 bis 6, wobei das Set zumindest zwei oder mehr Nucleinsäuren umfasst, die in der Lage sind, spezifisch an zumindest zwei oder mehr Polynucleotide zu binden, die jeweils aus allen Magenkrebsmarkern nach Anspruch 5 ausgewählt sind.
 
8. Verwendung nach Anspruch 1 oder 2, wobei es sich um die Verwendung einer Vorrichtung handelt, die eine Nucleinsäure/Nucleinsäuren umfasst, die in der Lage ist/sind, spezifisch an ein Polynucleotid des Magenkrebsmarkers miR-4257 zu binden.
 
9. Verwendung nach Anspruch 8, wobei die Nucleinsäure ein Polynucleotid ist, das aus der aus folgenden Polynucleotiden (a) bis (e) bestehenden Gruppe ausgewählt ist:

(a) einem Polynucleotid, das aus einer Nucleotidsequenz mit SEQ ID No. 1 oder einer von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz besteht, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(b) einem Polynucleotid, das eine Nucleotidsequenz mit SEQ ID No. 1 umfasst;

(c) einem Polynucleotid, das aus einer Nucleotidsequenz besteht, die in Bezug auf eine Nucleotidsequenz mit SEQ ID No. 1 oder eine von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz komplementär ist, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(d) einem Polynucleotid, das eine Nucleotidsequenz umfasst, die in Bezug auf eine Nucleotidsequenz mit SEQ ID No. 1 oder eine von der Nucleotidsequenz durch das Ersetzen von u durch t abgeleitete Nucleotidsequenz komplementär ist, und

(e) einem Polynucleotid, das unter stringenten Bedingungen an ein beliebiges der Polynucleotide (a) bis (d) hybridisiert.


 
10. Verwendung nach Anspruch 8 oder 9, wobei die Vorrichtung außerdem eine Nucleinsäure/Nucleinsäuren umfasst, die spezifisch an zumindest ein oder mehrere Polynucleotide bindet/binden, die aus der aus folgenden Magenkrebsmarkern bestehenden Gruppe ausgewählt sind: miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-Sp, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-428, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 und miR-671-5p und/oder
miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, miR-486-3p, miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507,miR-3141 und miR-1199-5p.
 
11. Verwendung nach Anspruch 10, wobei die Nucleinsäure ein Polynucleotid ist, das aus der aus folgenden Polynucleotiden (a') bis (e') bestehenden Gruppe ausgewählt ist:

(a') einem Polynucleotid, das aus einer Nucleotidsequenz mit einer beliebigen der SEQ ID No. 2 bis 165 und 635 bis 642 oder einer von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz besteht, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(b') einem Polynucleotid, das eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 2 bis 165 und 635 bis 642 umfasst;

(c') einem Polynucleotid, das aus einer Nucleotidsequenz besteht, die in Bezug auf eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 2 bis 165 und 635 bis 642 oder eine von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz komplementär ist, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(d') einem Polynucleotid, das eine Nucleotidsequenz umfasst, die in Bezug auf eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 2 bis 165 und 635 bis 642 oder eine von der Nucleotidsequenz durch das Ersetzen von u durch t abgeleitete Nucleotidsequenz komplementär ist, und

(e') einem Polynucleotid, das unter stringenten Bedingungen an ein beliebiges der Polynucleotide (a') bis (d') hybridisiert; und/oder

ein Polynucleotid ist, das aus der aus folgenden Polynucleotiden (f) bis (o) bestehenden Gruppe ausgewählt ist:

(f) einem Polynucleotid, das aus einer Nucleotidsequenz mit einer beliebigen der SEQ ID No. 166 bis 169 oder einer von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz besteht, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(g) einem Polynucleotid, das eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 166 bis 169 umfasst;

(h) einem Polynucleotid, das aus einer Nucleotidsequenz besteht, die in Bezug auf eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 166 bis 169 oder eine von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz komplementär ist, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(i) einem Polynucleotid, das eine Nucleotidsequenz umfasst, die in Bezug auf eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 166 bis 169 oder eine von der Nucleotidsequenz durch das Ersetzen von u durch t abgeleitete Nucleotidsequenz komplementär ist, und

(j) einem Polynucleotid, das unter stringenten Bedingungen an ein beliebiges der Polynucleotide (f) bis (i) hybridisiert;

(k) einem Polynucleotid, das aus einer Nucleotidsequenz mit einer beliebigen der SEQ ID No. 170 bis 199 oder einer von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz besteht, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(l) einem Polynucleotid, das eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 170 bis 199 umfasst;

(m) einem Polynucleotid, das aus einer Nucleotidsequenz besteht, die in Bezug auf eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 170 bis 199 oder eine von der Nucleotidsequenz durch Ersetzen von u durch t abgeleiteten Nucleotidsequenz komplementär ist, oder einer Variante, einem Derivat oder einem Fragment davon, das 15 oder mehr aufeinander folgende Nucleotide umfasst;

(n) einem Polynucleotid, das eine Nucleotidsequenz umfasst, die in Bezug auf eine Nucleotidsequenz mit einer beliebigen der SEQ ID No. 170 bis 199 oder eine von der Nucleotidsequenz durch das Ersetzen von u durch t abgeleitete Nucleotidsequenz komplementär ist, und

(o) einem Polynucleotid, das unter stringenten Bedingungen an ein beliebiges der Polynucleotide (k) bis (n) hybridisiert.


 
12. Verwendung nach einem der Ansprüche 8 bis 11, wobei die Vorrichtung eine Vorrichtung zur Messung durch ein Hybridisierungsverfahren ist.
 
13. Verwendung nach Anspruch 12, wobei das Hybridisierungsverfahren ein Nucleinsäure-Array-Verfahren ist.
 
14. Verwendung nach einem der Ansprüche 8 bis 13, wobei die Vorrichtung zumindest zwei oder mehr Nucleinsäuren umfasst, die in der Lage sind, spezifisch an zumindest zwei oder mehr Polynucleotide zu binden, die jeweils aus allen Magenkrebsmarkern nach Anspruch 10 ausgewählt sind.
 
15. Verfahren zur Detektion von Magenkrebs, das Folgendes umfasst: das Messen des Expressionsausmaßes einer Zielnucleinsäure/von Zielnucleinsäuren in einer Probe von einem Individuum unter Verwendung eines wie in einem der Ansprüche 3 bis 7 definierten Sets oder einer wie in einem der Ansprüche 8 bis 14 definierten Vorrichtung und das Bewerten in vitro, ob das Individuum Magenkrebs hat oder nicht, indem das/die gemessene(n) Ex-pressionsausmaß(e) und Kontrollexpressionsausmaß(e) in einer Probe von einem gesunden Individuum, die auf dieselbe Weise gemessen wurden, verwendet werden, wobei die Zielnucleinsäure/n das Magenkrebsmarker-Polynucleotid miR-4257 umfassen.
 
16. Verfahren nach Anspruch 15, wobei die Zielnucleinsäure/n außerdem zumindest ein oder mehrere Polynucleotide umfassen, die aus der aus folgenden Magenkrebsmarkern bestehenden Gruppe ausgewählt sind:
miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-,296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 und miR-671-5p, und/oder
zumindest ein oder mehrere Polynucleotide, die aus der aus weiteren Magenkrebsmarkern bestehenden Gruppe ausgewählt sind:
miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, miR-486-3p, miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 und miR-1199-5p.
 
17. Verfahren nach Anspruch 15 oder 16, wobei das Individuum ein Mensch ist.
 
18. Verfahren nach einem der Ansprüche 15 bis 17, wobei die Probe Blut, Serum oder Plasma ist.
 


Revendications

1. Utilisation d'un polynucléotide de marqueur du cancer de l'estomac miR-4257 dans un procédé in vitro de détection ou de diagnostic du cancer de l'estomac.
 
2. Utilisation selon la revendication 1, dans laquelle miR-4257 est utilisé avec au moins un ou plusieurs polynucléotide(s) sélectionné(s) dans le groupe consistant en les marqueurs du cancer de l'estomac : miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 et miR-671-5p, et/ou ;
au moins un ou plusieurs polynucléotide(s) sélectionné(s) dans le groupe consistant en d'autres marqueurs du cancer de l'estomac miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, miR-486-3p, miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 et miR-1199-5p.
 
3. Utilisation selon la revendication 1 ou la revendication 2, qui est l'utilisation d'un kit comprenant un/des acide(s) nucléique(s) capable(s) de spécifiquement se lier à un polynucléotide de marqueur du cancer de l'estomac miR-4257.
 
4. Utilisation selon la revendication 3, dans laquelle l'acide nucléique est un polynucléotide sélectionné dans le groupe consistant en les polynucléotides (a) à (e) suivants :

(a) un polynucléotide consistant en une séquence de nucléotides représentée par SEQ ID NO: 1 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(b) un polynucléotide comprenant une séquence de nucléotides représentée par SEQ ID NO: 1,

(c) un polynucléotide consistant en une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par SEQ ID NO: 1 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(d) un polynucléotide comprenant une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par SEQ ID NO: 1 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, et

(e) un polynucléotide qui s'hybride dans des conditions stringentes à l'un quelconque des polynucléotides (a) à (d) .


 
5. Utilisation selon la revendication 3 ou 4, dans laquelle le kit comprend en outre un/des acide(s) nucléique(s) capable(s) de spécifiquement se lier à au moins un ou plusieurs polynucléotides sélectionnés dans le groupe consistant en les autres marqueurs du cancer de l'estomac suivants : miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 et miR-671-5p, et/ou ;
miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, miR-486-3p, miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 et miR-1199-5p.
 
6. Utilisation selon la revendication 5, dans laquelle l'acide nucléique est un polynucléotide sélectionné dans le groupe consistant en les polynucléotides (a') à (e') suivants :

(a') un polynucléotide consistant en une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 2 à 165 et 635 à 642 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(b') un polynucléotide comprenant une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 2 à 165 et 635 à 642,

(c') un polynucléotide consistant en une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par SEQ ID NO: 2 à 165 et 635 à 642 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(d') un polynucléotide comprenant une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 2 à 165 et 635 à 642 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, et (e') un polynucléotide qui s'hybride dans des conditions stringentes à l'un quelconque des polynucléotides (a) à (d'), et/ou ;

un polynucléotide sélectionné dans le groupe consistant en les polynucléotides (f) à (o) suivants :

(f) un polynucléotide consistant en une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 166 à 169 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(g) un polynucléotide comprenant une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 166 à 169,

(h) un polynucléotide consistant en une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 166 à 169 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(i) un polynucléotide comprenant une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 166 à 169 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t,

(j) un polynucléotide qui s'hybride dans des conditions stringentes à l'un quelconque des polynucléotides (f) à (i),

(k) un polynucléotide consistant en une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 170 à 199 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(l) un polynucléotide comprenant une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 170 à 199,

(m) un polynucléotide consistant en une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 170 à 199 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(n) un polynucléotide comprenant une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 170 à 199 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, et

(o) un polynucléotide qui s'hybride dans des conditions stringentes à l'un quelconque des polynucléotides (k) à (n).


 
7. Utilisation selon l'une quelconque des revendications 3 à 6, dans laquelle le kit comprend au moins deux acides nucléiques ou plus capables de spécifiquement se lier à au moins deux polynucléotides ou plus, respectivement, sélectionnés parmi tous les marqueurs du cancer de l'estomac selon la revendication 5.
 
8. Utilisation selon la revendication 1 ou la revendication 2, qui est l'utilisation d'un dispositif comprenant un/des acide(s) nucléique(s) capable(s) de spécifiquement se lier à un polynucléotide de marqueur du cancer de l'estomac : miR-4257.
 
9. Utilisation selon la revendication 8, dans laquelle l'acide nucléique est un polynucléotide sélectionné dans le groupe consistant en les polynucléotides (a) à (e) suivants :

(a) un polynucléotide consistant en une séquence de nucléotides représentée par SEQ ID NO: 1 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(b) un polynucléotide comprenant une séquence de nucléotides représentée par SEQ ID NO: 1,

(c) un polynucléotide consistant en une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par SEQ ID NO: 1 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(d) un polynucléotide comprenant une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par SEQ ID NO: 1 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, et

(e) un polynucléotide qui s'hybride dans des conditions stringentes à l'un quelconque des polynucléotides (a) à (d).


 
10. Utilisation selon la revendication 8 ou 9, dans laquelle le dispositif comprend en outre un/des acide (s) nucléique(s) capable(s) de spécifiquement se lier à au moins un ou plusieurs polynucléotides sélectionnés dans le groupe consistant en les autres marqueurs du cancer de l'estomac suivants : miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 et miR-671-5p, et/ou ;
miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, miR-486-3p, miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 et miR-1199-5p.
 
11. Utilisation selon la revendication 10, dans laquelle l'acide nucléique est un polynucléotide sélectionné dans le groupe consistant en les polynucléotides (a') à (e') suivants :

(a') un polynucléotide consistant en une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 2 à 165 et 635 à 642 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(b') un polynucléotide comprenant une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 2 à 165 et 635 à 642,

(c') un polynucléotide consistant en une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par SEQ ID NO: 2 à 165 et 635 à 642 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(d') un polynucléotide comprenant une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 2 à 165 et 635 à 642 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, et (e') un polynucléotide qui s'hybride dans des conditions stringentes à l'un quelconque des polynucléotides (a) à (d'), et/ou ;

un polynucléotide sélectionné dans le groupe consistant en les polynucléotides (f) à (o) suivants :

(f) un polynucléotide consistant en une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 166 à 169 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(g) un polynucléotide comprenant une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 166 à 169,

(h) un polynucléotide consistant en une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 166 à 169 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(i) un polynucléotide comprenant une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 166 à 169 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t,

(j) un polynucléotide qui s'hybride dans des conditions stringentes à l'un quelconque des polynucléotides (f) à (i),

(k) un polynucléotide consistant en une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 170 à 199 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(l) un polynucléotide comprenant une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 170 à 199,

(m) un polynucléotide consistant en une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 170 à 199 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, un variant de celle-ci, un dérivé de celle-ci, ou un fragment de celle-ci comprenant 15 nucléotides consécutifs ou plus,

(n) un polynucléotide comprenant une séquence de nucléotides complémentaire à une séquence de nucléotides représentée par l'une quelconque de SEQ ID NO: 170 à 199 ou une séquence de nucléotides dérivée de la séquence de nucléotides par le remplacement de u par t, et

(o) un polynucléotide qui s'hybride dans des conditions stringentes à l'un quelconque des polynucléotides (k) à (n) .


 
12. Utilisation selon l'une quelconque des revendications 8 à 11, dans laquelle le dispositif est un dispositif pour une mesure par une technique d'hybridation.
 
13. Utilisation selon la revendication 12, dans laquelle la technique d'hybridation est une technique par réseau d'acide nucléique.
 
14. Utilisation selon l'une quelconque des revendications 8 à 13, dans laquelle le dispositif comprend au moins deux acides nucléiques ou plus capables de spécifiquement se lier à au moins deux polynucléotides ou plus, respectivement, sélectionnés parmi tous les marqueurs du cancer de l'estomac selon la revendication 10.
 
15. Procédé de détection du cancer de l'estomac, comprenant la mesure d'un/de taux d'expression d'un/d'acide(s) nucléique(s) cible(s) dans un échantillon d'un sujet en utilisant le kit défini dans l'une quelconque des revendications 3 à 7 ou le dispositif défini dans l'une quelconque des revendications 8 à 14, et l'évaluation in vitro du fait que le sujet souffre ou non du cancer de l'estomac en utilisant à la fois le(s) taux d'expression mesuré(s) et un/des taux d'expression de contrôle dans un échantillon d'un sujet en bonne santé mesuré(s) de la même manière, où le/les acide(s) nucléique(s) cible(s) comprend/comprennent le polynucléotide de marqueur du cancer de l'estomac miR-4257.
 
16. Procédé selon la revendication 15, dans lequel le/les acide(s) nucléique(s) cible(s) comprend/comprennent en outre au moins un ou plusieurs polynucléotide(s) sélectionné(s) dans le groupe consistant en les marqueurs du cancer de l'estomac : miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089 et miR-671-5p, et/ou ;
au moins un ou plusieurs polynucléotide(s) sélectionné(s) dans le groupe consistant en d'autres marqueurs du cancer de l'estomac miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, miR-486-3p, miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 et miR-1199-5p.
 
17. Procédé selon la revendication 15 ou la revendication 16, dans lequel le sujet est un humain.
 
18. Procédé selon l'une quelconque des revendications 15 à 17, dans lequel l'échantillon est du sang, du sérum, ou du plasma.
 




Drawing

















Cited references

REFERENCES CITED IN THE DESCRIPTION



This list of references cited by the applicant is for the reader's convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.

Patent documents cited in the description




Non-patent literature cited in the description