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. 2021 Jan 19:10:562019.
doi: 10.3389/fonc.2020.562019. eCollection 2020.

MiRNA Polymorphisms and Hepatocellular Carcinoma Susceptibility: A Systematic Review and Network Meta-Analysis

Qimeng Zhang  1 , Xueying Xu  1 , Mingcheng Wu  1 , Tiantian Qin  1 , Shaoning Wu  1 , Hongbo Liu  1
Affiliations

MiRNA Polymorphisms and Hepatocellular Carcinoma Susceptibility: A Systematic Review and Network Meta-Analysis

Qimeng Zhang et al. Front Oncol. .

Abstract

Background: Hepatocellular 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).

Methods: Databases 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.

Results: A 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.

Conclusion: MiR-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.

Keywords: hepatitis B virus; hepatocellular carcinoma; microRNA; network meta-analysis; polymorphism; susceptibility.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA Flow diagram of the literature during the review process for the systematic review and meta-analysis.
Figure 2
Figure 2
Risk of bias assessment using the Newcastle-Ottawa Scale for case-control studies.
Figure 3
Figure 3
Forest plots of the association of four single nucleotide polymorphisms (SNPs) and hepatocellular carcinoma (HCC) risk. (A) miR-146a rs2910164; (B) miR-149 rs2292832; (C) miR-196a2 rs11614913; (D) miR-499 rs3746444.
Figure 4
Figure 4
Forest plots of the association of four single nucleotide polymorphisms (SNPs) under different hepatitis B virus (HBV) infection status in hepatocellular carcinoma (HCC) patients.
Figure 5
Figure 5
Begg’ funnel plots of publication bias. (A) miR-146a rs2910164; (B) miR-196a2 rs11614913; (C) miR-499 rs3746444.
Figure 6
Figure 6
The network evidence plot of four single nucleotide polymorphisms (SNPs).
See this image and copyright information in PMC

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