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MicroRNAs as novel biomarkers for pancreatic cancer diagnosis: a meta-analysis based on 18 articles

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Tumor Biology

Abstract

Dysregulated microRNAs (miRNAs) have been reported to be associated with pancreatic cancer (PaC), suggesting that they may serve as useful novel diagnostic biomarkers for PaC. Various studies have been performed to investigate the diagnostic value of miRNAs for PaC but have obtained conflicting results. Therefore, this meta-analysis aims to comprehensively and quantitatively evaluate the potential diagnostic value of miRNAs for PaC. We systematically searched PubMed, Embase, Google Scholar, Cochrane Library, and Chinese National Knowledge Infrastructure for publications concerning the diagnostic value of miRNAs for PaC without language restriction. The quality of each study was scored using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The summary receiver operator characteristic curve and other parameters were applied to check the overall test performance. Heterogeneity was tested with the I 2 test and publication bias was tested with the Deek’s funnel plot asymmetry test. This meta-analysis included 18 articles with a total of 2,036 patients and 1,444 controls. The pooled sensitivity was 82 % (95 % CI, 78–86 %); the specificity was 77 % (95 % CI, 73–81 %); the PLR was 3.6 (95 % CI, 3.0–4.4); the NLR was 0.23 (95 % CI, 0.18–0.29); the DOR was 16 (95 % CI, 10–24); and the AUC was 0.86 (95 % CI, 0.83–0.89). Subgroups analyses were also performed and revealed that there were significant differences between some subgroups: the multiple-miRNAs profiling-based assays, non-blood-based assays, and healthy control-based studies all showed higher accuracies in diagnosing PaC than that of their counterparts. This meta-analysis suggests that the use of miRNAs has potential diagnostic value with a relatively high sensitivity and specificity for PaC, particularly the use of multiple miRNAs for discriminating PaC patients from healthy individuals. More prospective studies on the diagnostic value of miRNAs for PaC are needed in the future.

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References

  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.

    Article  PubMed  Google Scholar 

  2. Mann DV, Edwards R, Ho S, Lau WY, Glazer G. Elevated tumour marker CA19-9: clinical interpretation and influence of obstructive jaundice. Eur J Surg Oncol. 2000;26:474–9.

    Article  CAS  PubMed  Google Scholar 

  3. Schmidt C. Early detection tools for pancreatic cancer. J Natl Cancer Inst. 2012;104:1117–8.

    Article  PubMed  Google Scholar 

  4. Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;24:5313–27.

    Article  CAS  PubMed  Google Scholar 

  5. Poruk KE, Gay DZ, Brown K, Mulvihill JD, Boucher KM, Scaife CL, et al. The clinical utility of CA 19-9 in pancreatic adenocarcinoma: diagnostic and prognostic updates. Curr Mol Med. 2013;13:340–51.

    PubMed Central  CAS  PubMed  Google Scholar 

  6. Flynt AS, Lai EC. Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet. 2008;9:831–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Ouimet M, Moore KJ. A big role for small RNAs in HDL homeostasis. J Lipid Res. 2013;54:1161–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99:15524–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Navon R, Wang H, Steinfeld I, Tsalenko A, Ben-Dor A, Yakhini Z. Novel rank-based statistical methods reveal microRNAs with differential expression in multiple cancer types. PLoS One. 2009;4:e8003.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56:1733–41.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Ryu JK, Matthaei H, Dal Molin M, Hong SM, Canto MI, Schulick RD, et al. Elevated microRNA miR-21 levels in pancreatic cyst fluid are predictive of mucinous precursor lesions of ductal adenocarcinoma. Pancreatology. 2011;11:343–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Munding JB, Adai AT, Maghnouj A, Urbanik A, Zollner H, Liffers ST, et al. Global microRNA expression profiling of microdissected tissues identifies miR-135b as a novel biomarker for pancreatic ductal adenocarcinoma. Int J Cancer. 2012;131:E86–95.

    Article  CAS  PubMed  Google Scholar 

  14. Schultz NA, Werner J, Willenbrock H, Roslind A, Giese N, Horn T, et al. MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma. Mod Pathol. 2012;25:1609–22.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. Liu JQ, Gao J, Ren Y, Wang XW, Wang WW, Lu H. Diagnostic value of plasma miR-21 in pancreatic cancer. World Chinese Journal of Digestology. 2011;19:860–3.

    CAS  Google Scholar 

  17. Zhang J, Zhao CY, Zhang SH, Yu DH, Chen Y, Liu QH, et al. Upregulation of miR-194 contributes to tumor growth and progression in pancreatic ductal adenocarcinoma. Oncol Rep. 2014;31:1157–64.

    CAS  PubMed  Google Scholar 

  18. Ganepola GA, Rutledge JR, Suman P, Yiengpruksawan A, Chang DH. Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer. World J Gastrointest Oncol. 2014;6:22–33.

    Article  PubMed Central  PubMed  Google Scholar 

  19. 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.

    Article  PubMed  Google Scholar 

  20. Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol. 2005;58:982–90.

    Article  PubMed  Google Scholar 

  21. Deeks JJ. Systematic reviews in health care: systematic reviews of evaluations of diagnostic and screening tests. BMJ. 2001;323:157–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  PubMed  Google Scholar 

  23. Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M. MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J Gastrointest Surg. 2008;12:2171–6.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Habbe N, Koorstra JB, Mendell JT, Offerhaus GJ, Ryu JK, Feldmann G, et al. MicroRNA miR-155 is a biomarker of early pancreatic neoplasia. Cancer Biol Ther. 2009;8:340–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Morimura R, Komatsu S, Ichikawa D, Takeshita H, Tsujiura M, Nagata H, et al. Novel diagnostic value of circulating miR-18a in plasma of patients with pancreatic cancer. Br J Cancer. 2011;105:1733–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Bauer AS, Keller A, Costello E, Greenhalf W, Bier M, Borries A, et al. Diagnosis of pancreatic ductal adenocarcinoma and chronic pancreatitis by measurement of microRNA abundance in blood and tissue. PLoS One. 2012;7:e34151.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Liu J, Gao J, Du Y, Li Z, Ren Y, Gu J, et al. Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer. Int J Cancer. 2012;131:683–91.

    Article  CAS  PubMed  Google Scholar 

  28. Liu R, Chen X, Du Y, Yao W, Shen L, Wang C, et al. Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer. Clin Chem. 2012;58:610–8.

    Article  CAS  PubMed  Google Scholar 

  29. Ren Y, Gao J, Liu JQ, Wang XW, Gu JJ, Huang HJ, et al. Differential signature of fecal microRNAs in patients with pancreatic cancer. Mol Med Rep. 2012;6:201–9.

    CAS  PubMed  Google Scholar 

  30. Li A, Yu J, Kim H, Wolfgang CL, Canto MI, Hruban RH, et al. MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls. Clin Cancer Res. 2013;19:3600–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Wang WS, Liu LX, Li GP, Chen Y, Li CY, Jin DY, et al. Combined serum CA19-9 and miR-27a-3p in peripheral blood mononuclear cells to diagnose pancreatic cancer. Cancer Prev Res (Phila). 2013;6:331–8.

    Article  CAS  Google Scholar 

  32. Zhao C, Zhang J, Zhang S, Yu D, Chen Y, Liu Q, et al. Diagnostic and biological significance of microRNA-192 in pancreatic ductal adenocarcinoma. Oncol Rep. 2013;30:276–84.

    CAS  PubMed  Google Scholar 

  33. 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.

    Article  CAS  PubMed  Google Scholar 

  34. Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg. 1997;225:621–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Real FX. A “catastrophic hypothesis” for pancreas cancer progression. Gastroenterology. 2003;124:1958–64.

    Article  PubMed  Google Scholar 

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Correspondence to Haorong Wu.

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Ding, Z., Wu, H., Zhang, J. et al. MicroRNAs as novel biomarkers for pancreatic cancer diagnosis: a meta-analysis based on 18 articles. Tumor Biol. 35, 8837–8848 (2014). https://doi.org/10.1007/s13277-014-2133-4

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  • DOI: https://doi.org/10.1007/s13277-014-2133-4

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