Tumor Biology

, Volume 36, Issue 4, pp 2559–2567 | Cite as

Predictive power of circulating miRNAs in detecting colorectal cancer

  • Wei Zeng
  • Yanhui Tu
  • Yufeng Zhu
  • Zhongli Wang
  • Chi Li
  • Lijun Lao
  • Gang Wu
Research Article


Many studies indicate that circulating microRNAs (miRNAs) could play important roles in screening human cancers, including colorectal cancer (CRC). However, the conflicting results on the accuracy of miRNA detection lead us to conduct this meta-analysis to access the predictive value of miRNAs for predicting CRC. Eligible studies were identified from the Medline, Embase, CNKI, and Web of Science by the search strategies and screening criterion. We used random effects models to calculate the pooled results from studies. The summary receiver operator characteristic curve (SROC) and the area under the SROC curve (AUC) were used to estimate the predictive accuracy. Subgroup analyses and meta-regression were used to analyze potential sources of heterogeneity. We used Deeks’ funnel plot asymmetry test to test publication bias. This meta-analysis included a total of 24 studies from 19 articles, including 1558 CRC patients and 1085 controls. The overall pooled results from the meta-analysis were as follows: sensitivity was 0.81 (95 % confidence interval (CI) 0.77–0.85), specificity was 0.84 (95 % CI 0.78–0.88), PLR was 5.0 (95 % CI 3.5–6.9), NLR was 0.22 (95 % CI 0.18–0.28), DOR was 23 (95 % CI 14–37), and AUC was 0.89 (95 % CI 0.86–0.91). Subgroup and meta-regression analyses demonstrated that multiple miRNAs (AUC, sensitivity, and specificity of 0.92, 0.84, and 0.87, respectively) had a higher predictive accuracy than single miRNA (AUC, sensitivity, and specificity of 0.84, 0.78, and 0.78, respectively). In addition, we found that serum can be a better matrix for miRNA assays in screening CRC compared with plasma. In summary, our data suggests that circulating miRNAs, particularly multiple miRNAs, which have higher accuracy than single miRNAs, are excellent biomarker for screening CRC with good sensitivity and noninvasive nature.


Colorectal cancer Circulating MicroRNAs Screening Meta-analysis 


Conflicts of interest



  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30. doi: 10.3322/caac.21166.CrossRefPubMedGoogle Scholar
  2. 2.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29. doi: 10.3322/caac.21208.CrossRefPubMedGoogle Scholar
  3. 3.
    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.CrossRefPubMedGoogle Scholar
  4. 4.
    DeSantis C, Naishadham D, Jemal A. Cancer statistics for African Americans, 2013. CA Cancer J Clin. 2013;63:151–66. doi: 10.3322/caac.21173.CrossRefPubMedGoogle Scholar
  5. 5.
    Fu JF, Huang YQ, Yang J, Yi CH, Chen HL, Zheng S. Clinical characteristics and prognosis of young patients with colorectal cancer in Eastern China. World J Gastroenterol. 2013;19:8078–84. doi: 10.3748/wjg.v19.i44.8078.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    O’Connell JB, Maggard MA, Ko CY. Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst. 2004;96:1420–5. doi: 10.1093/jnci/djh275.CrossRefPubMedGoogle Scholar
  7. 7.
    Burch JA, Soares-Weiser K, St John DJ, Duffy S, Smith S, Kleijnen J, et al. Diagnostic accuracy of faecal occult blood tests used in screening for colorectal cancer: a systematic review. J Med Screen. 2007;14:132–7. doi: 10.1258/096914107782066220.CrossRefPubMedGoogle Scholar
  8. 8.
    Hewitson P, Glasziou P, Irwig L, Towler B, Watson E. Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane Database Syst Rev. 2007. doi: 10.1002/14651858.CD001216.pub2.
  9. 9.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66. doi: 10.1038/nrc1997.CrossRefPubMedGoogle Scholar
  10. 10.
    Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006. doi: 10.1038/cr.2008.282.CrossRefPubMedGoogle Scholar
  11. 11.
    Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8. doi: 10.1073/pnas.0804549105.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wilmott JS, Zhang XD, Hersey P, Scolyer RA. The emerging important role of microRNAs in the pathogenesis, diagnosis and treatment of human cancers. Pathology. 2011;43:657–71. doi: 10.1097/PAT.0b013e32834a7358.CrossRefPubMedGoogle Scholar
  13. 13.
    He X, Dong Y, Wu CW, Zhao Z, Ng SS, Chan FK, et al. MicroRNA-218 inhibits cell cycle progression and promotes apoptosis in colon cancer by downregulating BMI1 polycomb ring finger oncogene. Mol Med. 2012;18:1491–8. doi: 10.2119/molmed.2012.00304.PubMedCentralGoogle Scholar
  14. 14.
    Zhang N, Li X, Wu CW, Dong Y, Cai M, Mok MT, et al. microRNA-7 is a novel inhibitor of YY1 contributing to colorectal tumorigenesis. Oncogene. 2013;32:5078–88.CrossRefPubMedGoogle Scholar
  15. 15.
    Ng EK, Chong WW, Jin H, Lam EK, Shin VY, Yu J, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut. 2009;58:1375–81. doi: 10.1136/gut.2008.167817.CrossRefPubMedGoogle Scholar
  16. 16.
    Zhang GJ, Zhou T, Liu ZL, Tian HP, Xia SS. Plasma miR-200c and miR-18a as potential biomarkers for the detection of colorectal carcinoma. Mol Clin Oncol. 2013;1:379–84.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Toiyama Y, Takahashi M, Hur K, Nagasaka T, Tanaka K, Inoue Y, et al. Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. J Natl Cancer Inst. 2013;105:849–59.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Pu XX, Huang GL, Guo HQ, Guo CC, Li H, Ye S, et al. Circulating miR-221 directly amplified from plasma is a potential diagnostic and prognostic marker of colorectal cancer and is correlated with p53 expression. J Gastroenterol Hepatol. 2010;25:1674–80. doi: 10.1111/j.1440-1746.2010.06417.x.CrossRefPubMedGoogle Scholar
  19. 19.
    Sheinerman KS, Tsivinsky VG, Umansky SR. Analysis of organ-enriched microRNAs in plasma as an approach to development of Universal Screening Test: feasibility study. J Transl Med. 2013;11.Google Scholar
  20. 20.
    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.CrossRefPubMedGoogle Scholar
  21. 21.
    Walter SD. Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data. Stat Med. 2002;21:1237–56. doi: 10.1002/sim.1099.CrossRefPubMedGoogle Scholar
  22. 22.
    Jones CM, Athanasiou T. Summary receiver operating characteristic curve analysis techniques in the evaluation of diagnostic tests. Ann Thorac Surg. 2005;79:16–20. doi: 10.1016/j.athoracsur.2004.09.040.CrossRefPubMedGoogle Scholar
  23. 23.
    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
  24. 24.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    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.CrossRefPubMedGoogle Scholar
  26. 26.
    Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X. Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer. 2010;127:118–26.CrossRefPubMedGoogle Scholar
  27. 27.
    Kanaan Z, Rai SN, Eichenberger MR, Roberts H, Keskey B, Pan J, et al. Plasma MiR-21: A potential diagnostic marker of colorectal cancer. Ann Surg. 2012;256:544–51.CrossRefPubMedGoogle Scholar
  28. 28.
    Liu HS, Ma YY, Xiao HS. The diagnostic value of serum microRNAs including miR-129-3p, miR-767-3p and miR-877* for colorectal cancer. Tumor. 2012;32:42–8.Google Scholar
  29. 29.
    Wang Q, Huang Z, Ni S, Xiao X, Xu Q, Wang L, et al. Plasma miR-601 and miR-760 are novel biomarkers for the early detection of colorectal cancer. PLoS ONE. 2012;7:e44398. doi: 10.1371/journal.pone.0044398.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Feng L, Pang Z, Sha S, Wu B, Xu F, Yin SP. The value of diagnosis and prognosis prediction of serum miR-29a and miR-92a for colorectal cancer. Chin J Clin Oncol Rehabil. 2013;1313–1315.Google Scholar
  31. 31.
    Giraldez MD, Lozano JJ, Ramirez G, Hijona E, Bujanda L, Castells A, et al. Circulating microRNAs as biomarkers of colorectal cancer: results from a genome-wide profiling and validation study. Clin Gastroenterol Hepatol. 2013;11:681–688.e683.CrossRefPubMedGoogle Scholar
  32. 32.
    Kanaan Z, Roberts H, Eichenberger MR, Billeter A, Ocheretner G, Pan J, et al. A plasma microRNA panel for detection of colorectal adenomas: a step toward more precise screening for colorectal cancer. Ann Surg. 2013;258:400–8. doi: 10.1097/SLA.0b013e3182a15bcc.CrossRefPubMedGoogle Scholar
  33. 33.
    Liu GH, Zhou ZG, Chen R, Wang MJ, Zhou B, Li Y, et al. Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer. Tumour Biol. 2013;34:2175–81. doi: 10.1007/s13277-013-0753-8.CrossRefPubMedGoogle Scholar
  34. 34.
    Luo X, Stock C, Burwinkel B, Brenner H. Identification and evaluation of plasma microRNAs for early detection of colorectal cancer. PLoS ONE. 2013;8:e62880. doi: 10.1371/journal.pone.0062880.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Wang S, Xiang J, Li Z, Lu S, Hu J, Gao X, et al. A plasma microRNA panel for early detection of colorectal cancer. Int J Cancer. 2013. doi: 10.1002/ijc.28136.Google Scholar
  36. 36.
    Yong FL, Law CW, Wang CW. Potentiality of a triple microRNA classifier: MiR-193a-3p, miR-23a and miR-338-5p for early detection of colorectal cancer. BMC Cancer. 2013;13.Google Scholar
  37. 37.
    Wang J, Huang SK, Zhao M, Yang M, Zhong JL, Gu YY, et al. Identification of a circulating MicroRNA signature for colorectal cancer detection. PLoS ONE. 2014;9:e87451. doi: 10.1371/journal.pone.0087451.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Zanutto S, Pizzamiglio S, Ghilotti M, Bertan C, Ravagnani F, Perrone F, et al. Circulating miR-378 in plasma: a reliable, haemolysis-independent biomarker for colorectal cancer. Br J Cancer. 2014;110:1001–7. doi: 10.1038/bjc.2013.819.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Zhang L, Meng L, Fan Z, Liu B, Pei Y, Zhao Z. Expression of plasma miR-106a in colorectal cancer and its clinical significance. Nan Fang Yi Ke Da Xue Xue Bao. 2014;34:354–7.PubMedGoogle Scholar
  40. 40.
    Wu CW, Dong YJ, Ng S, Leung WW, Wong CY, Sung JJ, et al. Identification of a panel of MicroRNAs in stool as screening markers for colorectal cancer. Gastroenterology. 2011;140:S73.CrossRefGoogle Scholar
  41. 41.
    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.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Wei Zeng
    • 1
  • Yanhui Tu
    • 2
  • Yufeng Zhu
    • 1
  • Zhongli Wang
    • 1
  • Chi Li
    • 1
  • Lijun Lao
    • 1
  • Gang Wu
    • 1
  1. 1.General Surgery DepartmentThe First Affiliated Hospital of Liaoning Medical UniversityJinzhouChina
  2. 2.Laboratory of Molecular MedicineLiaoning Medical UniversityJinzhouChina

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