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MiRNA Polymorphisms and Cancer Prognosis: A Systematic Review and Meta-Analysis.

ABSTRACT: Background: Accumulating studies have focused on the relationship between miRNAs polymorphisms and cancer prognosis. However, the results are conflicting and unconvincing. This systematic review and meta-analysis was conducted to explore the relationship between miRNAs polymorphisms and cancer prognosis, aiming to seek for markers with cancer prognostic function. Methods: Hazard ratio of overall survival, disease-free survival (DFS) and recurrence-free survival were calculated to evaluate the association between miRNAs polymorphisms and cancer prognosis by using Stata software 11.0. Results: We systematically reviewed the association of 17 miRNAs SNPs with cancer prognosis including 24,721 samples. It was shown that 6 miRNAs SNPs (miR-608 rs4919510, miR-492 rs2289030, miR-378 rs1076064, miR-499 rs4919510, miR-149 rs2292832, miR-196a2 rs11614913) were associated with better cancer overall survival (OS) while let-7i rs10877887 was associated with poor OS; the homozygous and heterozygote genotype of miR-423 were related to poor cancer relapse-free survival (RFS) when compared with the wild genotype; miR-146 rs2910164 was linked to favorable cancer DFS while miR-196a2 rs11614913 was associated with poor DFS. Conclusions: In summary, let-7i rs10877887, miR-608 rs4919510, miR-492 rs2289030, miR-378 rs1076064, miR-423 rs6505162, miR-499 rs4919510, miR-149 rs2292832, miR-146 rs2910164, and miR-196a2 rs11614913 might serve as potential biomarkers for cancer prognosis.

SUBMITTER: Ding HX

PROVIDER: S-EPMC6300499 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Project description:BackgroundHepatocellular carcinoma (HCC) is an intractable public health threat worldwide, representing the second leading cause of cancer-related mortality, with limited early detection and therapeutic options. Recent findings have revealed that the susceptibility of HCC is closely related to microRNA (miRNA). We performed this systematic review with a network meta-analysis to investigated four single nucleotide polymorphisms (SNPs) that most regularly reported in miRNAs, exploring their involvement in HCC susceptibility and interaction with hepatitis B virus (HBV).MethodsDatabases were reviewed for related studies published up to May 2019 to identify all studies that compared genotypes of miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444 with no language and date restrictions. A pairwise meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals incorporating heterogeneity to assess the relationship between four miRNA polymorphisms and HCC. To further clarify the effect of polymorphisms on HCC, a Bayesian network meta-analysis was conducted to combine the effective sizes of direct and indirect comparisons. Calculations were performed by R version 3.6.1 and STATA 14.0. All steps were performed according to PRISMA guidelines.ResultsA total of 20 studies were enrolled in this network meta-analysis, providing 5,337 hepatocellular carcinoma cases and 6,585 controls. All included studies had an acceptable quality. Pairwise meta-analysis demonstrated that miR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, while the other three SNPs were not found to have a significant association. In the analysis of HCC patients under different HBV infection status, only miR-196a2 revealed correlation of threefold risk. The network results showed no significant difference in the distribution of genotype frequencies except for miR-196a2, which appeared to have the highest superiority index when comparing and ranking four SNPs.ConclusionMiR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, especially for HBV- related HCC, and that individuals with TC/CC were more susceptible. No significant association was found in the other three miRNA genes. MiR-196a2 could serve as the best predictor of susceptibility in HCC.

Project description: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. 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. 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. 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.

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MiRNA Polymorphisms and Cancer Prognosis: A Systematic Review and Meta-Analysis.

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