Genetic variant in DICER gene is associated with prognosis of hepatocellular carcinoma in a Chinese cohort

Hepatol Res. 2017 Aug;47(9):845-853. doi: 10.1111/hepr.12824. Epub 2016 Nov 7.

Abstract

Aim: MicroRNAs (miRNAs) function as gene regulators and play crucial roles in the pathogenesis and prognosis of hepatocellular carcinoma (HCC). Genetic variants in miRNA processing genes may affect miRNA expression and contribute to HCC risk and survival. We hypothesized that single nucleotide polymorphisms (SNPs) in miRNA processing genes may be associated with HCC susceptibility and prognosis. The study aims to verify whether this hypothesis is right or not.

Methods: We first genotyped the selected three SNPs in miRNA processing genes (RAN rs3803012 A>G, HIWI rs10773771 T>C, and DICER rs1057035 T>C) in 312 HCC patients and 320 cancer-free controls using the TaqMan assay, and evaluated the associations of the three SNPs with HCC risk. We also investigated the effect of the three SNPs on the overall survival of 312 HCC patients.

Results: There were no significant associations between the three SNPs (RAN rs3803012 A>G, HIWI rs10773771 T>C, and DICER rs1057035 T>C) and HCC risk. However, HCC patients carrying DICER rs1057035 CT + CC genotypes had significantly longer median survival time (log-rank, P = 0.018) and decreased death risk (adjusted hazard ratio = 0.68; 95% confidence interval, 0.49-0.95; P = 0.022) than patients with rs1057035 TT genotypes. The DICER rs1057035 genotype was an independent protective factor for HCC survival (CT + CC vs. TT: hazard ratio = 0.72; 95% confidence interval, 0.55-0.96; P = 0.031).

Conclusion: This study provides evidence that DICER rs1057035 T>C polymorphism may be a prognostic biomarker for HCC patients.

Keywords: DICER; hepatocellular carcinoma (HCC); microRNA; prognostic biomarker; single nucleotide polymorphism (SNP).