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Genetic Variants and Expression of Cytochrome P450 Oxidoreductase Predict Postoperative Survival in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma

Abstract

Our current study investigates the prognostic values of genetic variants and mRNA expression of cytochrome p450 oxidoreductase () in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A total of 19 candidate single nucleotide polymorphisms (SNPs) located in the exons of were genotyped using Sanger sequencing from 476 HBV-related HCC patients who underwent hepatectomy between 2003 and 2013. The mRNA expression of in 212 patients with HBV-related HCC was obtained from GSE14520 dataset. Survival analysis was performed to investigate the association of variants and mRNA expression with overall survival (OS) and recurrence-free survival (RFS). Nomograms were used to predict the prognosis of HBV-related HCC patients. Gene set enrichment analysis (GSEA) was used to investigate the mechanism of in HBV-related HCC prognosis. The polymorphism -rs1057868 was significantly associated with HBV-related HCC OS (CT/TT vs. CC, hazard ratio [HR] = 0.69, 95% confidence interval [CI] = [0.54, 0.88], = 0.003), but not significantly associated with RFS (CT/TT vs. CC, = 0.378). mRNA expression was also significantly associated with HBV-related HCC OS (high vs. low, HR = 0.61, 95% CI = [0.38, 0.97], = 0.036), but not significantly associated with the RFS (high vs. low, = 0.201). Two nomograms were developed to predict the HBV-related HCC OS. Furthermore, GSEA suggests that multiple gene sets were significantly enriched in liver cancer survival and recurrence, as well as -related target therapy in the liver. In conclusion, our study suggests that -rs1057868 and mRNA expression may serve as a potential postoperative prognosis biomarker in HBV-related HCC.

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