Genetic variants and Expression of Cytochrome p450 Oxidoreductase Predict Postoperative Survival in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma.

Huang K, Liao X, Han C, Wang X, Yu T, Yang C, Liu X, Yu L, Chen Z, Qin W, Zhu G, Su H, Liu Z, Zeng X, Zhou X, Lu S, Huang J, Liang Y, Liu Z, Deng J, Ye X, Peng T

J. Cancer 10 (6) 1453-1465 [2019-02-23; online 2019-02-23]

Our current study investigates the prognostic values of genetic variants and mRNA expression of cytochrome p450 oxidoreductase (POR) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A total of 19 candidate single nucleotide polymorphisms (SNPs) located in the exons of POR were genotyped using Sanger sequencing from 476 HBV-related HCC patients who underwent hepatectomy between 2003 and 2013. The mRNA expression of POR in 212 patients with HBV-related HCC was obtained from GSE14520 dataset. Survival analysis was performed to investigate the association of POR 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 POR in HBV-related HCC prognosis. The polymorphism POR-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], P = 0.003), but not significantly associated with RFS (CT/TT vs. CC, P = 0.378). POR mRNA expression was also significantly associated with HBV-related HCC OS (high vs. low, HR = 0.61, 95% CI = [0.38, 0.97], P = 0.036), but not significantly associated with the RFS (high vs. low, P = 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 POR-related target therapy in the liver. In conclusion, our study suggests that POR-rs1057868 and mRNA expression may serve as a potential postoperative prognosis biomarker in HBV-related HCC.

PubMed 31031855

DOI 10.7150/jca.28919

Crossref 10.7150/jca.28919

pmc: PMC6485213
pii: jcav10p1453