Comprehensive Analysis of the Expression and Prognosis of 12 Cytochrome P450s in Human Hepatocellular Carcinoma from the Perspective of Network Pharmacology

Abstract Background: Cytochrome P450s (CYPs) are pivotal drug metabolic enzymes and play a crucial part in the development and prognosis of hepatocellular carcinoma (HCC). Among various CYPs, 12 (CYP1A2, 27A1, 2A6, 2A7, 2B6, 2C8, 2C9, 2E1, 2J2, 3A4, 3A5, and 4A11) are recognized as key therapeutic targets for HCC from the perspective of network pharmacology. However, the gene expression and prognosis of these 12 CYPs in HCC remain obscure.Methods: In the current study, the mRNA expression of these 12 CYPs and survival of patients with HCC were investigated by mining data from ONCOMINE, Kaplan–Meier plotter, UALCAN, Human Protein Atlas, cBioPortal, STRING, and DAVID databases. Network pharmacology analysis of sorafenib for HCC treatment was conducted using data from Therapeutic Target Database, Drugbank, Swiss Target Prediction, STITCH, OncoDB.HCC, Liverome, STRING, and DAVID databases.Results: Results showed that the mRNA expression levels of the 12 CYPs were markedly reduced in HCC and negatively correlated with tumor stages and grades (except for CYP3A5). The high expression level of nine CYPs, namely, CYP27A1, 2A6, 2A7, 2C8, 2C9, 2E1, 3A4, 3A5, and 4A11 was significantly correlated with favorable prognosis in patients with HCC, indicating that they may serve as candidate prognostic biomarkers for HCC. Additionally, overexpression of CYP27A1, CYP2A7, CYP2B6, CYP2C9, and CYP3A5 was markedly correlated with favorable overall survival in HCC patients who received sorafenib therapy. Network pharmacology analysis of the administration of sorafenib for HCC treatment suggested that this drug may exert its antihepatocarcinoma effects by regulating the FoxO and ErbB signaling pathways.Conclusion: Characterization of the expression and prognosis of 12 CYPs in HCC, as well as network pharmacology analysis of HCC treatment via sorafenib, may provide novel insights into the discovery of potential prognostic markers of and therapeutic targets in HCC.