Tumor Biology

, Volume 35, Issue 12, pp 11995–12004 | Cite as

Diagnostic value of circulating microRNAs for gastric cancer in Asian populations: a meta-analysis

  • Lihua Liu
  • Shan Wang
  • Xiutang Cao
  • Jianchao Liu
Research Article


Gastric cancer (GC) accounts for one of the highest mortality worldwide and particularly in East Asia. Many studies have reported on the potential value of microRNAs (miRNAs) detection for diagnosing GC, but their results have proven inconclusive. The present meta-analysis was conducted to assess the diagnostic value of circulating miRNAs for GC diagnosis. A literature search was carried out in databases (PubMed, Embase, Web of Science, The Cochrane Library, and CNKI) and other sources using combinations of keywords relating to GC, miRNAs, and diagnosis. The values of sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR) reported in individual studies were pooled using random-effects models. Potential sources of heterogeneity were assessed with subgroup and meta-regression analyses. The summary receiver operating characteristic (SROC) curve and the area under the curve (AUC) were used to assess the diagnosis accuracy of miRNAs. This meta-analysis included 1,279 patients with GC and 954 healthy controls from 20 publications. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.78 (95 % CI: 0.73–0.81), 0.80 (95 % CI: 0.76–0.84), 4.0 (95 % CI: 3.1–6.0), 0.28 (95 % CI: 0.23–0.34), 14 (95 % CI: 10–21), and 0.86 (95 % CI: 0.83–0.89), respectively. Subgroup analyses showed that early stages (I and II) GC were more easily detected than later stages and that multiple miRNAs assays were more accurate than single miRNA assays. Our meta-analysis suggests that miRNAs have a high diagnostic value for GC, especially in its early stages (I and II). In addition, multiple miRNAs assays have a better diagnosis value than single miRNA assays. In conclusion, circulating miRNAs might be used as noninvasive biomarkers for the confirmation of GC detection in Asian populations.


Circulating MicroRNAs Gastric cancer Diagnosis Meta-analysis 


Conflicts of interest



  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi: 10.3322/caac.20107.PubMedCrossRefGoogle Scholar
  2. 2.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917. doi: 10.1002/ijc.25516.PubMedCrossRefGoogle Scholar
  3. 3.
    Lurje G, Schiesser M, Claudius A, Schneider PM. Circulating tumor cells in gastrointestinal malignancies: current techniques and clinical implications. J Oncol. 2010;2010:392652. doi: 10.1155/2010/392652.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Song MY, Pan KF, Su HJ, Zhang L, Ma JL, Li JY, et al. Identification of serum microRNAs as novel non-invasive biomarkers for early detection of gastric cancer. PLoS One. 2012;7:e33608. doi: 10.1371/journal.pone.0033608.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Hisaoka M, Matsuyama A, Nagao Y, Luan L, Kuroda T, Akiyama H, et al. Identification of altered microRNA expression patterns in synovial sarcoma. Genes Chromosome Cancer. 2011;50:137–45. doi: 10.1002/gcc.20837.CrossRefGoogle Scholar
  6. 6.
    Martin 2nd RC, Jaques DP, Brennan MF, Karpeh M. Extended local resection for advanced gastric cancer: increased survival versus increased morbidity. Ann Surg. 2002;236:159–65. doi: 10.1097/01.SLA.0000022023.28027.5C.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Leung WK, Wu MS, Kakugawa Y, Kim JJ, Yeoh KG, Goh KL, et al. Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 2008;9:279–87. doi: 10.1016/S1470-2045(08)70072-X.PubMedCrossRefGoogle Scholar
  8. 8.
    Hoskovec D, Varga J, Konecna E, Antos F. Levels of CEA and Ca 19-9 in the sera and peritoneal cavity in patients with gastric and pancreatic cancers. Acta Cir Bras. 2012;27:410–6.PubMedGoogle Scholar
  9. 9.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66. doi: 10.1038/nrc1997.PubMedCrossRefGoogle Scholar
  10. 10.
    He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435:828–33. doi: 10.1038/nature03552.PubMedCrossRefGoogle Scholar
  11. 11.
    Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8. doi: 10.1038/nature03702.PubMedCrossRefGoogle Scholar
  12. 12.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.PubMedCrossRefGoogle Scholar
  13. 13.
    Hu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol. 2010;28:1721–6. doi: 10.1200/JCO.2009.24.9342.PubMedCrossRefGoogle Scholar
  14. 14.
    Chen Q, Ge X, Zhang Y, Xia H, Yuan D, Tang Q, et al. Plasma miR-122 and miR-192 as potential novel biomarkers for the early detection of distant metastasis of gastric cancer. Oncol Rep. 2014;31:1863–70. doi: 10.3892/or.2014.3004.PubMedGoogle Scholar
  15. 15.
    Xu Q, Dong QG, Sun LP, He CY, Yuan Y. Expression of serum miR-20a-5p, let-7a, and miR-320a and their correlations with pepsinogen in atrophic gastritis and gastric cancer: a case-control study. BMC Clin Pathol. 2013;13:11. doi: 10.1186/1472-6890-13-11.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Wang B, Zhang Q. The expression and clinical significance of circulating microRNA-21 in serum of five solid tumors. J Cancer Res Clin Oncol. 2012;138:1659–66. doi: 10.1007/s00432-012-1244-9.PubMedCrossRefGoogle Scholar
  17. 17.
    Khalili M, Sadeghizadeh M, Ghorbanian K, Malekzadeh R, Vasei M, Mowla SJ. Down-regulation of miR-302b, an ESC-specific microRNA, in gastric adenocarcinoma. Cell J. 2012;13:251–8.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Zheng Y, Cui L, Sun W, Zhou H, Yuan X, Huo M, et al. MicroRNA-21 is a new marker of circulating tumor cells in gastric cancer patients. Cancer Biomark. 2011;10:71–7. doi: 10.3233/cbm-2011-0231.PubMedGoogle Scholar
  19. 19.
    Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, Kosuga T, et al. Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer. 2010;102:1174–9. doi: 10.1038/sj.bjc.6605608.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Shiotani A, Murao T, Kimura Y, Matsumoto H, Kamada T, Kusunoki H, et al. Identification of serum miRNAs as novel non-invasive biomarkers for detection of high risk for early gastric cancer. Br J Cancer. 2013;109:2323–30. doi: 10.1038/bjc.2013.596.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Li BS, Zhao YL, Guo G, Li W, Zhu ED, Luo X, et al. Plasma microRNAs, miR-223, miR-21 and miR-218, as novel potential biomarkers for gastric cancer detection. PLoS One. 2012;7:e41629. doi: 10.1371/journal.pone.0041629.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36. doi: 10.7326/0003-4819-155-8-201110180-00009.PubMedCrossRefGoogle Scholar
  23. 23.
    Deville WL, Buntinx F, Bouter LM, Montori VM, de Vet HC, van der Windt DA, et al. Conducting systematic reviews of diagnostic studies: didactic guidelines. BMC Med Res Methodol. 2002;2:9.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.PubMedCrossRefGoogle Scholar
  25. 25.
    Dinnes J, Deeks J, Kirby J, Roderick P. A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy. Health Technol Assess. 2005;9:1–113. iii.CrossRefGoogle Scholar
  26. 26.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60. doi: 10.1136/bmj.327.7414.557.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol. 2005;58:882–93. doi: 10.1016/j.jclinepi.2005.01.016.PubMedCrossRefGoogle Scholar
  28. 28.
    Zhu C, Ren C, Han J, Ding Y, Du J, Dai N, et al. A five-microRNA panel in plasma was identified as potential biomarker for early detection of gastric cancer. Br J Cancer. 2014. doi: 10.1038/bjc.2014.119.Google Scholar
  29. 29.
    Peng WZ, Ma R, Wang F, Yu J, Liu ZB. Role of miR-191/425 cluster in tumorigenesis and diagnosis of gastric cancer. Int J Mol Sci. 2014;15:4031–48. doi: 10.3390/ijms15034031.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Li C, Li JF, Cai Q, Qiu QQ, Yan M, Liu BY, et al. miRNA-199a-3p in plasma as a potential diagnostic biomarker for gastric cancer. Ann Surg Oncol. 2013;20 Suppl 3:S397–405. doi: 10.1245/s10434-012-2600-3.PubMedCrossRefGoogle Scholar
  31. 31.
    Li C, Li JF, Cai Q, Qiu QQ, Yan M, Liu BY, et al. MiRNA-199a-3p: a potential circulating diagnostic biomarker for early gastric cancer. J Surg Oncol. 2013;108:89–92. doi: 10.1002/jso.23358.PubMedCrossRefGoogle Scholar
  32. 32.
    Cai H, Yuan Y, Hao YF, Guo TK, Wei X, Zhang YM. Plasma microRNAs serve as novel potential biomarkers for early detection of gastric cancer. Med Oncol. 2013;30:452. doi: 10.1007/s12032-012-0452-0.PubMedCrossRefGoogle Scholar
  33. 33.
    Li YQ, Huang PW, Zhu CJ, Chen CP, Cheng T, Li JY. Diagnostic value of expressions of miR-27a and miR-18b for early detection of gastric cancer. JIangsu Med J. 2012;38:1665–7.Google Scholar
  34. 34.
    Zhou H, Xiao B, Zhou F, Deng H, Zhang X, Lou Y, et al. MiR-421 is a functional marker of circulating tumor cells in gastric cancer patients. Biomarkers. 2012;17:104–10. doi: 10.3109/1354750x.2011.614961.PubMedCrossRefGoogle Scholar
  35. 35.
    Liu H, Zhu L, Liu B, Yang L, Meng X, Zhang W, et al. Genome-wide microRNA profiles identify miR-378 as a serum biomarker for early detection of gastric cancer. Cancer Lett. 2012;316:196–203. doi: 10.1016/j.canlet.2011.10.034.PubMedCrossRefGoogle Scholar
  36. 36.
    Konishi H, Ichikawa D, Komatsu S, Shiozaki A, Tsujiura M, Takeshita H, et al. Detection of gastric cancer-associated microRNAs on microRNA microarray comparing pre- and post-operative plasma. Br J Cancer. 2012;106:740–7. doi: 10.1038/bjc.2011.588.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Zhu CJ, Zhang JY, Wei J, Liu YQ, Su YQ. MiR-191 and miR-27a in plasma are promising novel biomarkers for detection of gastric cancer. Acta Univ Med Nanjing (Nat Sci). 2011;31:1173–8.Google Scholar
  38. 38.
    Liu R, Zhang C, Hu Z, Li G, Wang C, Yang C, et al. A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur J Cancer. 2011;47:784–91. doi: 10.1016/j.ejca.2010.10.025.PubMedCrossRefGoogle Scholar
  39. 39.
    Zhou H, Guo JM, Lou YR, Zhang XJ, Zhong FD, Jiang Z, et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker. J Mol Med (Berlin). 2010;88:709–17. doi: 10.1007/s00109-010-0617-2.CrossRefGoogle Scholar
  40. 40.
    di Mario F, Cavallaro LG. Non-invasive tests in gastric diseases. Dig Liver Dis. 2008;40:523–30. doi: 10.1016/j.dld.2008.02.028.PubMedCrossRefGoogle Scholar
  41. 41.
    Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006;24:2903–9. doi: 10.1200/JCO.2005.05.0245.PubMedCrossRefGoogle Scholar
  42. 42.
    Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PM. The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol. 2003;56:1129–35.PubMedCrossRefGoogle Scholar
  43. 43.
    Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654–9. doi: 10.1038/ncb1596.PubMedCrossRefGoogle Scholar
  44. 44.
    Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007;450:1235–9. doi: 10.1038/nature06385.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Lihua Liu
    • 1
  • Shan Wang
    • 2
  • Xiutang Cao
    • 1
  • Jianchao Liu
    • 1
  1. 1.Institute of Hospital Management and ResearchChinese PLA General HospitalBeijingChina
  2. 2.Department of Epidemiology and Biostatistics, Institute of Basic Medical SciencesPeking Union Medical College/Chinese Academy of Medical SciencesBeijingChina

Personalised recommendations