The prognostic value of CYP2C subfamily genes in hepatocellular carcinoma

Abstract

Cytochrome P2C (CYP2C) subfamily members (CYP2C8, CYP2C9, CYP2C18, and CYP2C19) are known to participate in clinical drug metabolism. However, the association between CYP2C subfamily members and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic value of CYP2C subfamily gene expression levels with HCC prognosis. Data of 360 HCC patients in The Cancer Genome Atlas database and 231 in the Gene Expression Omnibus database were analyzed. Kaplan–Meier analysis and a Cox regression model were used to ascertain overall survival and recurrence-free survival, and to calculate median survival time using hazard ratios (HR) and 95% confidence intervals (CI). In TCGA database, low expression of CYP2C8, CYP2C9, and CYP2C19 in tumor tissue was associated with a short median survival time (all crude P = 0.001, adjusted P = 0.004, P = 0.047, and P = 0.020, respectively). In TCGA database, joint effects analysis of the combinations of CYP2C8 and CYP2C9, CYP2C8 and CYP2C19, and CYP2C9 and CYP2C19 revealed that high expression of two genes (group 4; group IV, group d) was associated with a reduced risk of death as compared to low expression (group 1, group I, and group a) (adjusted P = 0.005, P = 0.013, and P = 0.016, respectively). In TCGA database, joint effects analysis of CYP2C8, CYP2C9, and CYP2C19 showed that the risk of death from HCC was lower for groups C and D than for group A (adjusted P = 0.012 and P = 0.008, respectively). CYP2C8, CYP2C9, and CYP2C19 gene expression levels are potential prognostic markers of HCC following hepatectomy.

The results of this study indicate that CYP2C8, CYP2C9, and CYP2C19 present potential serum biomarkers for the early diagnosis of HCC. Combination analysis showed significant interactions that were better prognostic indicators of HCC.

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