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miRNA Predictors of Pancreatic Cancer Chemotherapeutic Response: A Systematic Review and Meta-Analysis

School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, India
University of Adelaide, Adelaide, SA 5005, Australia
Genesis Cancer Care Centre, Bunbury, WA 6014, Australia
National Heart Institute, New Delhi 110065, India
Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
College of Health and Human Sciences, Yellow 1.1.05, Ellengowan Drive, Charles Darwin University, Darwin, NT 0909, Australia
Author to whom correspondence should be addressed.
Cancers 2019, 11(7), 900;
Received: 7 May 2019 / Revised: 13 June 2019 / Accepted: 21 June 2019 / Published: 27 June 2019
(This article belongs to the Special Issue New Biomarkers in Cancers)
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Background: pancreatic cancer (PC) has increasing incidence and mortality in developing countries, and drug resistance is a significant hindrance to the efficacy of successful treatment. The objective of this systematic review and meta-analysis was to evaluate the association between miRNAs and response to chemotherapy in pancreatic cancer patients. Methods: the systematic review and meta-analysis was based on articles collected from a thorough search of PubMed and Science Direct databases for publications spanning from January 2008 to December 2018. The articles were screened via a set of inclusion and exclusion criteria based on the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Data was extracted, collated and tabulated in MS Excel for further synthesis. Hazard ratio (HR) was selected as the effect size metric to be pooled across studies for the meta-analysis, with the random effects model being applied. Subgroup analysis was also conducted, and the presence of publication bias in the selected studies was assessed. Publication bias of the included studies was quantified. Findings: of the 169 articles screened, 43 studies were included in our systematic review and 13 articles were included in the meta-analysis. Gemcitabine was observed to be the principal drug used in a majority of the studies. A total of 48 miRNAs have been studied, and 18 were observed to have possible contributions to chemoresistance, while 15 were observed to have possible contributions to chemosensitivity. 41 drug-related genetic pathways have been identified, through which the highlighted miRNA may be affecting chemosensitivity/resistance. The pooled HR value for overall survival was 1.603; (95% Confidence Interval (CI) 1.2–2.143; p-value: 0.01), with the subgroup analysis for miR-21 showing HR for resistance of 2.061; 95% CI 1.195–3.556; p-value: 0.09. Interpretation: our results highlight multiple miRNAs that have possible associations with modulation of chemotherapy response in pancreatic cancer patients. Further studies are needed to discover the molecular mechanisms underlying these associations before they can be suggested for use as biomarkers of response to chemotherapeutic interventions in pancreatic cancer. View Full-Text
Keywords: pancreatic cancer; systematic review; meta-analysis; chemoresistance; miRNAs pancreatic cancer; systematic review; meta-analysis; chemoresistance; miRNAs

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Madurantakam Royam, M.; Ramesh, R.; Shanker, R.; Sabarimurugan, S.; Kumarasamy, C.; Ramesh, N.; Gothandam, K.M.; Baxi, S.; Gupta, A.; Krishnan, S.; Jayaraj, R. miRNA Predictors of Pancreatic Cancer Chemotherapeutic Response: A Systematic Review and Meta-Analysis. Cancers 2019, 11, 900.

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