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Erschienen in: Tumor Biology 9/2014

01.09.2014 | Research Article

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

verfasst von: Zhongyang Ding, Haorong Wu, Jiaming Zhang, Guorong Huang, Dongdong Ji

Erschienen in: Tumor Biology | Ausgabe 9/2014

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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.
Literatur
1.
2.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
3.
Zurück zum Zitat Schmidt C. Early detection tools for pancreatic cancer. J Natl Cancer Inst. 2012;104:1117–8.CrossRefPubMed Schmidt C. Early detection tools for pancreatic cancer. J Natl Cancer Inst. 2012;104:1117–8.CrossRefPubMed
4.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
5.
Zurück zum Zitat 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.PubMedCentralPubMed 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.PubMedCentralPubMed
8.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
9.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
10.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
11.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
12.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
13.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
14.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
15.
Zurück zum Zitat 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.CrossRef 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.CrossRef
16.
Zurück zum Zitat 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. 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.
17.
Zurück zum Zitat 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.PubMed 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.PubMed
18.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
19.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
20.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
21.
22.
Zurück zum Zitat Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.CrossRefPubMed Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.CrossRefPubMed
23.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
24.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
25.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
26.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
27.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
28.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
29.
Zurück zum Zitat 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.PubMed 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.PubMed
30.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
31.
Zurück zum Zitat 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.CrossRef 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.CrossRef
32.
Zurück zum Zitat 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.PubMed 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.PubMed
33.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
34.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
35.
Zurück zum Zitat Real FX. A “catastrophic hypothesis” for pancreas cancer progression. Gastroenterology. 2003;124:1958–64.CrossRefPubMed Real FX. A “catastrophic hypothesis” for pancreas cancer progression. Gastroenterology. 2003;124:1958–64.CrossRefPubMed
Metadaten
Titel
MicroRNAs as novel biomarkers for pancreatic cancer diagnosis: a meta-analysis based on 18 articles
verfasst von
Zhongyang Ding
Haorong Wu
Jiaming Zhang
Guorong Huang
Dongdong Ji
Publikationsdatum
01.09.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 9/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2133-4

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