Tingdong Yu, Xiangkun Wang, Guangzhi Zhu, Chuangye Han, Hao Su, Xiwen Liao, Chengkun Yang, Wei Qin, Ketuan Huang, Tao Peng

The activities of four cytochrome P3A (CYP3A) subfamily members (CYP3A4, CYP3A5, CYP3A7, and CYP3A43) are well documented in drug metabolism. However, the association between CYP3A subfamily members and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic value of CYP3A subfamily mRNA expression levels with HCC prognosis. Data from a total of 360 HCC patients were retrieved from The Cancer Genome Atlas database, and data from 231 HCC patients were retrieved from the Gene Expression Omnibus database. Kaplan-Meier analysis and Cox regression models were utilized to determine median survival, overall survival, and recurrence-free survival. Hazard ratios and 95% CI were calculated. Low expression of CYP3A4, CYP3A5, and CYP3A43 in the tumor tissue was associated with short median survival (crude p=0.004, 0.001, and 0.001; adjusted p=0.022, 0.005, and 0.013, respectively). Joint-effects combination analysis of CYP3A4, CYP3A5/CYP3A4, CYP3A43/CYP3A5, and CYP3A43 revealed that high expression groups of two genes (group C, group c, group 3) were associated with a reduced risk of death, as compared to low expression of two genes (group A, group a, group 1), and the adjusted p values were 0.001, 0.004, and 0.001, respectively. Joint-effects analysis of CYP3A4, CYP3A5, and CYP3A43 showed that groups III and IV had a reduced risk of death, as compared to group I (adjusted p=0.024 and 0.002, respectively). CYP3A4, CYP3A5, and CYP3A43 mRNA expression levels are potential prognostic markers of HCC.