Abstract
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.
Highlights
The GLOBOCAN 2018 data estimates that 18.1 million new cancer cases and 9.6 million cancer deaths occur worldwide
Our study aims to elucidate the relationship between miRNA expression and chemotherapeutic resistance or susceptibility in Pancreatic cancer (PC) through a systematic review and meta-analysis of extant literature
After full-text screening and applying inclusion criteria, a total of 43 studies with miRNA expression related chemosensitivity or chemoresistance totalling 1963 individuals with PC was obtained for this study
Summary
The GLOBOCAN 2018 data estimates that 18.1 million new cancer cases and 9.6 million cancer deaths occur worldwide. PC is the 12th most prevalent malignancy throughout the globe with 338,000 new cases recognised in 2012, and the five-year average prevalence rate was found to be 4.1 in 100,000 people throughout the world [2]. It has one of the lowest survival rates among the predominant tumours with a single digit five-year survival rate (2–9%) [3]. According to GLOBOCAN 2015 data, 1000 cases of PC are diagnosed daily [4], and 985 deaths [5] occur worldwide daily. The estimated annual PC burden in India in 2001 was 14,230 cases
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