Profiling cytochrome P450 family 4 gene expression in human hepatocellular carcinoma.

Abstract

Cytochrome P450 family 4 (CYP4) enzymes are known as microsomal omega (ω)-hydroxylases that metabolize fatty acids, eicosanoids, vitamin D and carcinogens. Thus, CYP4 enzymes may influence tumor development and progression. The aim of the present study was to evaluate the CYP4 expression profile in hepatocellular carcinoma (HCC) and its clinical relevance. The present study obtained CYP4 mRNA expression data for 377 HCC cases from The Cancer Genome Atlas cohort and performed Kaplan-Meier survival, Gene Ontology functional enrichment, and gene set enrichment analysis (GSEA). In addition, the level of CYP4F2 protein expression was evaluated in matched pairs of HCC and non-tumor tissue samples and the results were correlated with the clinicopathological characteristics of HCC (n=113). HCC survival analyses indicated better overall survival in patients with high CYP4F2, CYP4F12 and CYP4V2 mRNA expression levels; the results for histological grade and Tumor-Node-Metastasis stage supported these results. GSEA revealed high levels of CYP4F2, CYP4F12 and CYP4V2 mRNA expression to be negatively correlated with the expression of cell cycle-associated genes. CYP4F2 protein expression was higher in non-neoplastic liver tissue than in HCC tissue and positively correlated with favorable pathological tumor stage (I vs. II–IV; P=0.022) and was a good independent prognostic factor for overall survival (P=0.004). These results demonstrate that the expression levels of the genes CYP4F2, CYP4F12 and CYPV2 are favorable prognostic factors in HCC and suggest the potential predictive diagnostic and prognostic roles of CYP4F2, CYP4F12 and CYPV2 gene expression in HCC.