Detection of MicroRNA-21 Expression as a Potential Screening Biomarker for Colorectal Cancer: a Meta-analysis

  • Jiang, Jian-Xin (Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine) ;
  • Zhang, Na (Key Laboratory of Food Science and Engineering of Heilongjiang Province, Harbin University of Commerce) ;
  • Liu, Zhong-Min (Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine) ;
  • Wang, Yan-Ying (Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine)
  • Published : 2014.10.11


Background: Colorectal cancer (CRC) is a major cause of cancer-related death and cancer-related incidence worldwide. The potential of microRNA-21 (miR-21) as a biomarker for CRC detection has been studied in several studies. However, the results were inconsistent. Therefore, we conducted the present meta-analysis to systematically assess the diagnostic value of miR-21 for CRC. Materials and Methods: Using a random-effect model, the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to evaluate the diagnostic performance of miR-21 for CRC. A summary receiver operating characteristic (SROC) curve and an area under the curve (AUC) were also generated to assess the diagnosis accuracy of miR-21 for CRC. Q test and I2 statistics were used to assess between-study heterogeneity. Publication bias was evaluated by the Deeks' funnel plot asymmetry test. Results: A total of 986 CRC patients and 702 matched healthy controls from 8 studies were involved in the meta-analysis. The pooled results for SEN, SPE, PLR, NLR, DOR, and AUC were 57% (95%CI: 39%-74%), 87% (95%CI: 78%-93%), 4.4 (95%CI: 2.4-8.0), 0.49 (95%CI: 0.32-0.74), 9 (95%CI: 4-22), and 0.83 (95%CI: 0.79-0.86), respectively. Subgroup analyses further suggested that blood-based studies showed a better diagnostic accuracy compared with feces-based studies, indicating that blood may be a better matrix for miR-21 assay and CRC detection. Conclusions: Our findings suggest that miR-21 has a potential diagnostic value for CRC with a moderate level of overall diagnostic accuracy. Hence, it could be used as auxiliary means for the initial screening of CRC and avoid unnecessary colonoscopy, which is an invasive and expensive procedure.


  1. Ahlquist DA, Sargent DJ, Loprinzi CL, et al (2008). Stool DNA and occult blood testing for screen detection of colorectal neoplasia. Ann Intern Med, 149, 441-50.
  2. Asangani IA, Rasheed SA, Nikolova DA, et al (2008). MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene, 27, 2128-36.
  3. Chan SH, Wu CW, Li AF, et al (2008). miR-21 microRNA expression in human gastric carcinomas and its clinical association. Anticancer Res, 28, 907-11.
  4. Chang KH, Miller N, Kheirelseid EA, et al (2011). MicroRNA-21 and PDCD4 expression in colorectal cancer. Eur J Surg Oncol, 37, 597-603.
  5. Deeks JJ, Macaskill P and Irwig L (2005). The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol, 58, 882-93.
  6. Dinnes J, Deeks J, Kirby J, et al (2005). A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy. Health Technol Assess, 9, 1-113.
  7. Diosdado B, van de Wiel MA, Terhaar Sive Droste JS, et al (2009). MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression. Br J Cancer, 101, 707-14.
  8. Fakih MG and Padmanabhan A (2006). CEA monitoring in colorectal cancer. What you should know. Oncology, 20, 579-87.
  9. Glas AS, Lijmer JG, Prins MH, et al (2003). The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol, 56, 1129-35.
  10. Higgins JP, Thompson SG, Deeks JJ, et al (2003). Measuring inconsistency in meta-analyses. BMJ, 327, 557-60.
  11. Huang Q, Liu L, Liu CH, et al (2013). MicroRNA-21 regulates the invasion and metastasis in cholangiocarcinoma and may be a potential biomarker for cancer prognosis. Asian Pac J Cancer Prev, 14, 829-34.
  12. Huang Z, Huang D, Ni S, et al (2010). Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer, 127, 118-26.
  13. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al (2004). Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med, 351, 2704-14.
  14. Janakiram NB, Rao CV (2008). Molecular markers and targets for colorectal cancer prevention. Acta Pharmacol Sin, 29, 1-20.
  15. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  16. Kanaan Z, Rai SN, Eichenberger MR, et al (2012b). Plasma MiR-21: A potential diagnostic marker of colorectal cancer. Ann Surg, 256, 544-51.
  17. Koga Y, Yasunaga M, Takahashi A, et al (2010a). MicroRNA expression profiling of exfoliated colonocytes isolated from feces for colorectal cancer screening. Cancer Prev Res, 3, 1435-42.
  18. Koga Y, Yasunaga M, Takahashi A, et al (2010b). MicroRNA expression profiling of exfoliated colonocytes isolated from feces for colorectal cancer screening. Cancer Prev Res, 3, 1435-42.
  19. Kuriyama S, Hamaya Y, Yamada T, et al (2012). Fecal microrna assays as a marker for colorectal cancer screening. Gastroenterology, 142, 770.
  20. Lawrie CH, Gal S, Dunlop HM, et al (2008). Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol, 141, 672-5.
  21. Li Y, Li W, Ouyang Q, et al (2011). Detection of lung cancer with blood microRNA-21 expression levels in Chinese population. Oncol Lett, 2, 991-4.
  22. Liu GH, Zhou ZG, Chen R, et al (2013). Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer. Tumour Biol, 34, 2175-81.
  23. Luo X, Stock C, Burwinkel B, et al (2013). Identification and evaluation of plasma microRNAs for early detection of colorectal cancer. PLoS ONE, 8, 62880.
  24. Meng F, Henson R, Wehbe-Janek H, et al (2007). MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology, 133, 647-58.
  25. Monzo M, Navarro A, Bandres E, et al (2008). Overlapping expression of microRNAs in human embryonic colon and colorectal cancer. Cell Res, 18, 823-33.
  26. Nagel R, le Sage C, Diosdado B, et al (2008). Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer. Cancer Res, 68, 5795-802.
  27. Ng EK, Chong WW, Jin H, et al (2009). Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut, 58, 1375-81.
  28. O'Connell JB, Maggard MA and Ko CY (2004). Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst, 96, 1420-5.
  29. Pu XX, Huang GL, Guo HQ, et al (2010). 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, 25, 1674-80.
  30. Schetter AJ, Leung SY, Sohn JJ, et al (2008). MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA, 299, 425-36.
  31. Shibuya H, Iinuma H, Shimada R, et al (2010). Clinicopathological and prognostic value of microRNA-21 and microRNA-155 in colorectal cancer. Oncology, 79, 313-20.
  32. Slaby O, Svoboda M, Fabian P, et al (2007). Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology, 72, 397-402.
  33. Toiyama Y, Takahashi M, Hur K, et al (2013). Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. J Natl Cancer Inst, 105, 849-59.
  34. Wang Y, Gao X, Wei F, et al (2014). Diagnostic and prognostic value of circulating miR-21 for cancer: a systematic review and meta-analysis. Gene, 533, 389-97.
  35. Whiting PF, Rutjes AW, Westwood ME, et al (2011). QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med, 155, 529-36.
  36. Wu CW, Ng SSM, Dong YJ, et al (2012b). Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polyps. Gut, 61, 739-45.
  37. Xu YZ, Xi QH, Ge WL, et al (2013). Identification of serum microRNA-21 as a biomarker for early detection and prognosis in human epithelial ovarian cancer. Asian Pac J Cancer Prev, 14, 1057-60.
  38. Yamamichi N, Shimomura R, Inada K, et al (2009). Locked nucleic acid in situ hybridization analysis of miR-21 expression during colorectal cancer development. Clin Cancer Res, 15, 4009-16.
  39. Zanutto S, Pizzamiglio S, Ghilotti M, et al (2014). Circulating miR-378 in plasma: a reliable, haemolysis-independent biomarker for colorectal cancer. Br J Cancer, 110, 1001-7.
  40. Zeng Z, Wang J, Zhao L, et al (2013). Potential role of microRNA-21 in the diagnosis of gastric cancer: a metaanalysis. PLoS One, 8, 73278.
  41. Zhu S, Si ML, Wu H, et al (2007). MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem, 282, 14328-36.

Cited by

  1. Challenges of deciphering gastric cancer heterogeneity vol.21, pp.37, 2015,
  2. The role of circulating microRNAs as novel biomarkers in diagnosing colorectal cancer vol.27, pp.7, 2015,
  3. Icariin regulates the proliferation and apoptosis of human ovarian cancer cells through microRNA-21 by targeting PTEN, RECK and Bcl-2 vol.33, pp.6, 2015,
  4. MicroRNAs as Biomarkers in Colorectal Cancer vol.9, pp.9, 2017,
  5. Serum microRNA signatures and metabolomics have high diagnostic value in colorectal cancer using two novel methods vol.109, pp.4, 2018,