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Diagnostic value of circulating microRNAs as biomarkers for breast cancer: a meta-analysis study

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Tumor Biology

Abstract

Recent studies have provided new insights into the diagnostic value of circulating microRNAs (miRNAs) for breast cancer (BCa). However, the inconsistent results between studies have prevented the widespread usage of miRNAs in clinics. To systematically assess the potential diagnostic value of circulating miRNAs in BCa, we performed a comprehensive meta-analysis. Eligible studies were retrieved by searching electronic databases. The quality of the studies was assessed on the basis of quality assessment for studies of diagnostic accuracy (QUADAS) criteria. The bivariate meta-analysis model was employed to summarize the diagnostic indices and plot the summary receiver operator characteristic (SROC) curve. A total of 15 studies were included in this meta-analysis, involving 1368 BCa patients and 849 healthy controls. Our bivariate random effects meta-analysis yielded an area under curve (AUC) value of 0.9217, with a sensitivity of 0.82 (95 % confidence interval (CI) 0.80–0.83) and specificity of 0.82 (95 % CI 0.80–0.85) for the use of miRNAs in differentiating BCa patients from healthy controls. Notably, our subgroup analysis suggested that a combination of multiple miRNAs (AUC, sensitivity, and specificity of 0.9518, 0.87, and 0.88, respectively) seemed to harbor higher accuracy than single miRNA-based assays (AUC, sensitivity, and specificity of 0.8923, 0.79, and 0.77, respectively). Altogether, our data indicate that circulating miRNA profiling has a potential to be used as a screening test for BCa, among which, the detection of a combined multiple miRNAs may be a more comprehensive indicator than individual miRNA.

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References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30. doi:10.3322/caac.21166.

    Article  PubMed  Google Scholar 

  2. Cuk K, Zucknick M, Madhavan D, Schott S, Golatta M, Heil J, et al. Plasma microRNA panel for minimally invasive detection of breast cancer. PLoS One. 2013;8:e76729. doi:10.1371/journal.pone.0076729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Checka CM, Chun JE, Schnabel FR, Lee J, Toth H. The relationship of mammographic density and age: implications for breast cancer screening. AJR Am J Roentgenol. 2012;198:W292-5. doi:10.2214/AJR.10.6049.

    Article  PubMed  Google Scholar 

  4. Guadagni F, Ferroni P, Carlini S, Mariotti S, Spila A, Aloe S, et al. A reevaluation of carcinoembryonic antigen (CEA) as a serum marker for breast cancer: a prospective longitudinal study. Clin Cancer Res. 2001;7:2357–62.

    CAS  PubMed  Google Scholar 

  5. Duffy MJ, Evoy D, McDermott EW. CA 15-3: uses and limitation as a biomarker for breast cancer. Clin Chim Acta. 2010;411:1869–74.

    Article  CAS  PubMed  Google Scholar 

  6. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  PubMed  Google Scholar 

  7. Pritchard CC, Cheng HH, Tewari M. MicroRNA profiling: approaches and considerations. Nat Rev Genet. 2012;13:358–69. doi:10.1038/nrg3198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. Hamamoto J, Soejima K, Yoda S, Naoki K, Nakayama S, Satomi R, et al. Identification of microRNAs differentially expressed between lung squamous cell carcinoma and lung adenocarcinoma. Mol Med Rep. 2013;8:456–62. doi:10.3892/mmr.2013.1517.

    PubMed  Google Scholar 

  10. 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;13:280. doi:10.1186/1471-2407-13-280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Li W, Xie L, He X, Li J, Tu K, Wei L, et al. Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma. Int J Cancer. 2008;123:1616–22. doi:10.1002/ijc.23693.

    Article  CAS  PubMed  Google Scholar 

  12. Bovell LC, Putcha BD, Samuel T, Manne U. Clinical implications of microRNAs in cancer. Biotech Histochem. 2013;88:388–96. doi:10.3109/10520295.2013.788735.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chen WX, Hu Q, Qiu MT, Zhong SL, Xu JJ, Tang JH, et al. miR-221/222: promising biomarkers for breast cancer. Tumor Biol. 2013;34:1361–70. doi:10.1007/s13277-013-0750-y.

    Article  CAS  Google Scholar 

  14. Chen L, Li Y, Fu Y, Peng J, Mo MH, Stamatakos M, et al. Role of deregulated microRNAs in breast cancer progression using FFPE tissue. PLoS One. 2013;8:e54213. doi:10.1371/journal.pone.0054213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. 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.

    Article  CAS  PubMed  Google Scholar 

  17. Madhavan D, Cuk K, Burwinkel B, Yang R. Cancer diagnosis and prognosis decoded by blood-based circulating microRNA signatures. Front Genet. 2013;4:116. doi:10.3389/fgene.2013.00116.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Kubiczkova L, Kryukov F, Slaby O, Dementyeva E, Jarkovsky J, Nekvindova J, et al. Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance. Haematologica. 2014;99:511–8. doi:10.3324/haematol.2013.093500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wu Q, Wang C, Lu Z, Guo L, Ge Q. Analysis of serum genome-wide microRNAs for breast cancer detection. Clin Chim Acta. 2012;413:1058–65. doi:10.1016/j.cca.2012.02.016.

    Article  CAS  PubMed  Google Scholar 

  20. Schrauder MG, Strick R, Schulz-Wendtland R, Strissel PL, Kahmann L, Loehberg CR, et al. Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection. PLoS One. 2012;7:e29770. doi:10.1371/journal.pone.0029770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cuk K, Zucknick M, Heil J, Madhavan D, Schott S, Turchinovich A, et al. Circulating microRNAs in plasma as early detection markers for breast cancer. Int J Cancer. 2013;132:1602–12. doi:10.1002/ijc.27799.

    Article  CAS  PubMed  Google Scholar 

  22. Guo LJ, Zhang QY. Decreased serum miR-181a is a potential new tool for breast cancer screening. Int J Mol Med. 2012;30:680–6. doi:10.3892/ijmm.2012.1021.

    CAS  PubMed  Google Scholar 

  23. 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 

  24. Zeng RC, Zhang W, Yan XQ, Ye ZQ, Chen ED, Huang DP, et al. Down-regulation of miRNA-30a in human plasma is a novel marker for breast cancer. Med Oncol. 2013;30:477. doi:10.1007/s12032-013-0477-z.

    Article  PubMed  Google Scholar 

  25. Heneghan HM, Miller N, Kelly R, Newell J, Kerin MJ. Systemic miRNA-195 differentiates breast cancer from other malignancies and is a potential biomarker for detecting noninvasive and early stage disease. Oncologist. 2010;15:673–82. doi:10.1634/theoncologist.2010-0103.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mar-Aguilar F, Mendoza-Ramírez JA, Malagón-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 

  27. Zhao SY, Wu Q, Gao F, Zhang CB, Yang XW. Serum microRNA-155 as a potential biomarker for breast cancer screening. Chin Sci Bull. 2012;57:3466–8.

    Article  CAS  Google Scholar 

  28. Sun Y, Wang M, Lin G, Sun S, Li X, Qi J, et al. Serum microRNA-155 as a potential biomarker to track disease in breast cancer. PLoS One. 2012;7:e47003. doi:10.1371/journal.pone.0047003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hu Z, Dong J, Wang LE, Ma H, Liu J, Zhao Y, et al. Serum microRNA profiling and breast cancer risk: the use of miR-484/191 as endogenous controls. Carcinogenesis. 2012;33:828–34. doi:10.1093/carcin/bgs030.

    Article  CAS  PubMed  Google Scholar 

  30. Zhao FL, Hu GD, Wang XF, Zhang XH, Zhang YK, Yu ZS. Serum overexpression of microRNA-10b in patients with bone metastatic primary breast cancer. J Int Med Res. 2012;40:859–66.

    Article  CAS  PubMed  Google Scholar 

  31. 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 

  32. 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 

  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.

    Article  CAS  PubMed  Google Scholar 

  34. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62:1006–12. doi:10.1016/j.jclinepi.2009.06.005.

    Article  PubMed  Google Scholar 

  35. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003;3:25.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol. 2006;6:31.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Liu J, Mao Q, Liu Y, Hao X, Zhang S, Zhang J. Analysis of miR-205 and miR-155 expression in the blood of breast cancer patients. Chin J Cancer Res. 2013;25:46–54. doi:10.3978/j.issn.1000-9604.2012.11.04.

    PubMed  PubMed Central  Google Scholar 

  38. Roth C, Rack B, Müller V, Janni W, Pantel K, Schwarzenbach H. Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res. 2010;12:R90. doi:10.1186/bcr2766.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Shen Y, Wang T, Yang T, Hu Q, Wan C, Chen L, et al. Diagnostic value of circulating microRNAs for lung cancer: a meta-analysis. Genet Test Mol Biomarkers. 2013;17:359–66. doi:10.1089/gtmb.2012.0370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 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.

    Article  PubMed  Google Scholar 

  41. Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287–312.

    Article  CAS  PubMed  Google Scholar 

  42. Lv M, Zhu X, Chen W, Zhao J, Tang J. Searching for candidate microRNA biomarkers in detection of breast cancer: a meta-analysis. Cancer Biomark. 2013;13:395–401. doi:10.3233/CBM-130379.

    Article  CAS  PubMed  Google Scholar 

  43. Wang F, Hou J, Jin W, Li J, Yue Y, Jin H, et al. Increased circulating microRNA-155 as a potential biomarker for breast cancer screening: a meta-analysis. Molecules. 2014;19:6282–93. doi:10.3390/molecules19056282.

    Article  PubMed  Google Scholar 

  44. Wang K, Yuan Y, Cho JH, McClarty S, Baxter D, Galas DJ. Comparing the MicroRNA spectrum between serum and plasma. PLoS One. 2012;7:e41561. doi:10.1371/journal.pone.0041561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Zhao H, Shen J, Medico L, Wang D, Ambrosone CB, Liu S. A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer. PLoS One. 2010;5:e13735. doi:10.1371/journal.pone.0013735.

    Article  PubMed  PubMed Central  Google Scholar 

  46. 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.

    Article  PubMed  Google Scholar 

  47. Li Q, Liu L, Li W. Identification of circulating microRNAs as biomarkers in diagnosis of hematologic cancers: a meta-analysis. Tumour Biol. 2014. doi:10.1007/s13277-014-2364-4.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81371879).

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Authors and Affiliations

  1. Department of Clinical Laboratory, School of Medical Technology and Engineering, Fujian Medical University, 88 Jiaotong Road, Taijiang, Fuzhou, 350004, Fujian, China

    Zhaolei Cui, Donghong Lin, Wenfang Song, Meihuan Chen & Dan Li

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  1. Zhaolei Cui
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  2. Donghong Lin
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Correspondence to Donghong Lin.

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Cui, Z., Lin, D., Song, W. et al. Diagnostic value of circulating microRNAs as biomarkers for breast cancer: a meta-analysis study. Tumor Biol. 36, 829–839 (2015). https://doi.org/10.1007/s13277-014-2700-8

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