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Circulating microRNA-21 as a biomarker for the detection of various carcinomas: an updated meta-analysis based on 36 studies

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Tumor Biology

Abstract

Cancer is a class of diseases with high mortality rate, characterized by unregulated cell growth. Early diagnosis of cancer is currently the most effective method to prevent cancer development and improve the survival rate of patients. Traditional diagnostic methods such as biopsy usually provoke discomfort and unpleasant experience. Recently, microRNAs (miRNAs) were widely reported to be potential biomarkers to detect cancers without invasiveness. MicroRNA-21 (miRNA-21, miR-21) is one of the most prevalent miRNAs. This meta-analysis aims to make a comprehensive analysis of the potential role of circulating miR-21 as a biomarker in human carcinoma diagnosis. A total of 36 articles involving 2920 cancer patients and 1986 healthy controls with regard to the diagnostic value of the circulating miR-21 for cancer detection were selected from online bibliographic databases. For pooled analysis, the sensitivity, specificity, and other basic characteristics were extracted from the 36 included articles. Then, bivariate random-effects model was selected to gain pooled results. Furthermore, to explore the sources of heterogeneity, we conducted stratified and meta-regression analyses based on different race/sample groups. The pooled characteristics of all included articles were as follows: sensitivity, 0.78 (95 % confidence intervals (CI), 0.73–0.82); specificity, 0.82 (95 % CI, 0.79–0.86); positive likelihood ratio (PLR), 4.4 (95 % CI, 3.6–5.4); negative likelihood ratio (NLR), 0.26 (95 % CI, 0.21–0.33); diagnostic odds ratio (DOR), 17 (95 % CI, 12–24); and area under the curve (AUC), 0.87 (95 % CI, 0.84–0.90). The subgroup analyses results based on different ethnic populations revealed that the diagnostic accuracy of miR-21 tends to be higher in Asian populations than in Caucasian populations. Furthermore, another subgroup analysis performed on sample types suggested that the serum-based specimen used in cancer diagnosis appeared to be more accurate than the plasma-based specimen. Our meta-analysis shows that the circulating miR-21 may be a potential biomarker as diagnostic tool for early-stage cancer diagnosis.

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References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29. doi:10.3322/caac.20138.

    Article  PubMed  Google Scholar 

  2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96. doi:10.3322/CA.2007.0010.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  4. Mare L, Caretti A, Albertini R, Trinchera M. CA19.9 antigen circulating in the serum of colon cancer patients: where is it from? Int J Biochem Cell Biol. 2013;45:792–7. doi:10.1016/j.biocel.2013.01.004.

    Article  CAS  PubMed  Google Scholar 

  5. Sun W, Huang T, Li G, Shen W, Zhu J, Jin Q, et al. The advantage of circulating tumor cells over serum carcinoembryonic antigen for predicting treatment responses in rectal cancer. Future Oncol. 2013;9:1489–500. doi:10.2217/fon.13.91.

    Article  CAS  PubMed  Google Scholar 

  6. 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 

  7. Wu C, Wang C, Guan X, Liu Y, Li D, Zhou X, et al. Diagnostic and prognostic implications of a serum miRNA panel in oesophageal squamous cell carcinoma. PLoS One. 2014;9:e92292. doi:10.1371/journal.pone.0092292.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Schultz NA, Dehlendorff C, Jensen BV, Bjerregaard JK, Nielsen KR, Bojesen SE, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA. 2014;311:392–404. doi:10.1001/jama.2013.284664.

    Article  CAS  PubMed  Google Scholar 

  9. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31. doi:10.1038/nrg1379.

    Article  CAS  PubMed  Google Scholar 

  10. Hong L, Han Y, Zhang Y, Zhang H, Zhao Q, Wu K, et al. MicroRNA-21: a therapeutic target for reversing drug resistance in cancer. Expert Opin Ther Targets. 2013;17:1073–80. doi:10.1517/14728222.2013.819853.

    Article  CAS  PubMed  Google Scholar 

  11. Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27:2128–36. doi:10.1038/sj.onc.1210856.

    Article  CAS  PubMed  Google Scholar 

  12. Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, et al. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila). 2009;2:807–13. doi:10.1158/1940-6207.capr-09-0094.

    Article  CAS  Google Scholar 

  13. Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliano AE, Hoon DS. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem. 2011;57:84–91. doi:10.1373/clinchem.2010.151845.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    Article  PubMed  Google Scholar 

  15. Ouyang L, Liu P, Yang S, Ye S, Xu W, Liu X. A three-plasma miRNA signature serves as novel biomarkers for osteosarcoma. Med Oncol. 2013;30:340. doi:10.1007/s12032-012-0340-7.

    Article  PubMed  Google Scholar 

  16. Zeng Z, Wang J, Zhao L, Hu P, Zhang H, Tang X, et al. Potential role of microRNA-21 in the diagnosis of gastric cancer: a meta-analysis. PLoS One. 2013;8:e73278. doi:10.1371/journal.pone.0073278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wu R, Jiang Y, Wu Q, Li Q, Cheng D, Xu L, et al. Diagnostic value of microRNA-21 in the diagnosis of lung cancer: evidence from a meta-analysis involving 11 studies. Tumour Biol. 2014. doi:10.1007/s13277-014-2106-7.

    Google Scholar 

  18. Yang X, Guo Y, Du Y, Yang J, Li S, Liu S, et al. Serum microRNA-21 as a diagnostic marker for lung carcinoma: a systematic review and meta-analysis. PLoS One. 2014;9:e97460. doi:10.1371/journal.pone.0097460.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Liu Y, Chen JQ, Xie L, Wang J, Li T, He Y, et al. Effect of aspirin and other non-steroidal anti-inflammatory drugs on prostate cancer incidence and mortality: a systematic review and meta-analysis. BMC Med. 2014;12:55. doi:10.1186/1741-7015-12-55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hamza TH, Arends LR, van Houwelingen HC, Stijnen T. Multivariate random effects meta-analysis of diagnostic tests with multiple thresholds. BMC Med Res Methodol. 2009;9:73. doi:10.1186/1471-2288-9-73.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Li Y, Li W, Ouyang Q, Hu S, Tang J. Detection of lung cancer with blood microRNA-21 expression levels in Chinese population. Oncol Lett. 2011;2:991–4. doi:10.3892/ol.2011.351.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Liu JQ, Gao J, Ren Y, Wang XW, Wang WW, Lu H. [Diagnostic value of plasma miR-21 in pancreatic cancer]. World Chin J Digestol. 2011;19:860–3.

    CAS  Google Scholar 

  24. Shen J, Todd NW, Zhang H, Yu L, Lingxiao X, Mei Y, et al. Plasma microRNAs as potential biomarkers for non-small-cell lung cancer. Lab Invest. 2011;91:579–87. doi:10.1038/labinvest.2010.194.

    Article  CAS  PubMed  Google Scholar 

  25. Foss KM, Sima C, Ugolini D, Neri M, Allen KE, Weiss GJ. miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer. J Thorac Oncol. 2011;6:482–8. doi:10.1097/JTO.0b013e318208c785.

    Article  PubMed  Google Scholar 

  26. Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50:136–42. doi:10.1002/mc.20712.

    Article  CAS  PubMed  Google Scholar 

  27. Yaman Agaoglu F, Kovancilar M, Dizdar Y, Darendeliler E, Holdenrieder S, Dalay N, et al. Investigation of miR-21, miR-141, and miR-221 in blood circulation of patients with prostate cancer. Tumour Biol. 2011;32:583–8. doi:10.1007/s13277-011-0154-9.

    Article  CAS  PubMed  Google Scholar 

  28. 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.

    Article  CAS  PubMed  Google Scholar 

  29. Le HB, Zhu WY, Chen DD, He JY, Huang YY, Liu XG, et al. Evaluation of dynamic change of serum miR-21 and miR-24 in pre- and post-operative lung carcinoma patients. Med Oncol. 2012;29:3190–7. doi:10.1007/s12032-012-0303-z.

    Article  CAS  PubMed  Google Scholar 

  30. Chen X, Hu Z, Wang W, Ba Y, Ma L, Zhang C, et al. Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis. Int J Cancer. 2012;130:1620–8. doi:10.1002/ijc.26177.

    Article  CAS  PubMed  Google Scholar 

  31. Liu AM, Yao TJ, Wang W, Wong KF, Lee NP, Fan ST, et al. Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open. 2012;2:e000825. doi:10.1136/bmjopen-2012-000825.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Tomimaru Y, Eguchi H, Nagano H, Wada H, Kobayashi S, Marubashi S, et al. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol. 2012;56:167–75. doi:10.1016/j.jhep.2011.04.026.

    Article  CAS  PubMed  Google Scholar 

  33. 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.

    Article  CAS  PubMed  Google Scholar 

  34. Wang Q, Li P, Li A, Jiang W, Wang H, Wang J, et al. Plasma specific miRNAs as predictive biomarkers for diagnosis and prognosis of glioma. J Exp Clin Cancer Res. 2012;31:97. doi:10.1186/1756-9966-31-97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Xie H, Chu Z, Wang H. [Serum microRNA expression profile as a biomarker in diagnosis and prognosis of acute myeloid leukemia]. J Clin Pediatr. 2012;30:421–4.

    CAS  Google Scholar 

  36. Abd-El-Fattah AA, Sadik NA, Shaker OG, Aboulftouh ML. Differential microRNAs expression in serum of patients with lung cancer, pulmonary tuberculosis, and pneumonia. Cell Biochem Biophys. 2013;67:875–84. doi:10.1007/s12013-013-9575-y.

    Article  CAS  PubMed  Google Scholar 

  37. Gao J, Zhang Q, Xu J, Guo L, Li X. Clinical significance of serum miR-21 in breast cancer compared with CA153 and CEA. Chin J Cancer Res. 2013;25:743–8. doi:10.3978/j.issn. 1000-9604.2013.12.04.

    PubMed  PubMed Central  Google Scholar 

  38. Kishimoto T, Eguchi H, Nagano H, Kobayashi S, Akita H, Hama N, et al. Plasma miR-21 is a novel diagnostic biomarker for biliary tract cancer. Cancer Sci. 2013;104:1626–31. doi:10.1111/cas.12300.

    Article  CAS  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. Liu X, Luo HN, Tian WD, Lu J, Li G, Wang L et al. Diagnostic and prognostic value of plasma microRNA deregulation in nasopharyngeal carcinoma. Cancer Biol Ther. 2013;14.

  41. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ma J, Li N, Guarnera M, Jiang F. Quantification of plasma miRNAs by digital PCR for cancer diagnosis. Biomark Insights. 2013;8:127–36. doi:10.4137/bmi.s13154.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Mar-Aguilar F, Mendoza-Ramirez JA, Malagon-Santiago I, Espino-Silva PK, Santuario-Facio SK, Ruiz-Flores P, et al. Serum circulating microRNA profiling for identification of potential breast cancer biomarkers. Dis Markers. 2013;34:163–9. doi:10.3233/dma-120957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mozzoni P, Banda I, Goldoni M, Corradi M, Tiseo M, Acampa O, et al. Plasma and EBC microRNAs as early biomarkers of non-small-cell lung cancer. Biomarkers. 2013;18:679–86. doi:10.3109/1354750x.2013.845610.

    Article  CAS  PubMed  Google Scholar 

  45. Ng EK, Li R, Shin VY, Jin HC, Leung CP, Ma ES, et al. Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS One. 2013;8:e53141. doi:10.1371/journal.pone.0053141.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Qin Z, Zhu X, Huang Y. [Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma]. Sichuan Med J. 2013;34:1463–5.

    Google Scholar 

  47. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tang D, Shen Y, Wang M, Yang R, Wang Z, Sui A, et al. Identification of plasma microRNAs as novel noninvasive biomarkers for early detection of lung cancer. Eur J Cancer Prev. 2013;22:540–8. doi:10.1097/CEJ.0b013e32835f3be9.

    Article  CAS  PubMed  Google Scholar 

  49. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Liu SS, Wang YS, Sun YF, Miao LX, Wang J, Li YS, et al. Plasma microRNA-320, microRNA-let-7e and microRNA-21 as novel potential biomarkers for the detection of retinoblastoma. Biomed Rep. 2014;2:424–8. doi:10.3892/br.2014.246.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Mao X, Sun Y, Tang J. Serum miR-21 is a diagnostic and prognostic marker of primary central nervous system lymphoma. Neurol Sci. 2014;35:233–8.

    Article  PubMed  Google Scholar 

  52. Ye M, Ye P, Zhang W, Rao J, Xie Z. [Diagnostic values of salivary versus and plasma microRNA-21 for early esophageal cancer]. Nan Fang Yi Ke Da Xue Xue Bao. 2014;34:885–9.

    CAS  PubMed  Google Scholar 

  53. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Siyi Li.

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Kailiu Wu and Liwen Li contribute equally to this work.

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Wu, K., Li, L. & Li, S. Circulating microRNA-21 as a biomarker for the detection of various carcinomas: an updated meta-analysis based on 36 studies. Tumor Biol. 36, 1973–1981 (2015). https://doi.org/10.1007/s13277-014-2803-2

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  • DOI: https://doi.org/10.1007/s13277-014-2803-2

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