Role of CYP4F2 as a novel biomarker regulating malignant phenotypes of liver cancer cells via the Nrf2 signaling axis

Hepatocellular carcinoma (HCC) is one of the most prevalent types of cancer worldwide. The present study attempted to identify a prognostic biomarker for HCC. RNA sequencing data from the GSE63863 dataset were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified based on a protein-protein interaction (PPI) network, and prognostic evaluation was subsequently conducted. Following lentiviral transfection, the migratory, proliferative and apoptotic abilities of cells were evaluated using wound healing, Cell Counting Kit-8, Transwell migration and apoptosis assays. A total of 192 DEGs were identified from 11 pairs of HCC and matched non-tumor samples. The PPI network revealed the top three modules, and eight genes were identified from these modules. The expression levels of cytochrome P450 family 4 subfamily F member 2 (CYP4F2) were downregulated in 50 HCC samples from The Cancer Genome Atlas and in the HCC Hep3B cell line. Low CYP4F2 expression was associated with a lower overall survival time. Functional studies revealed that CYP4F2 overexpression inhibited HCC cell proliferation and migration, and induced apoptosis. Furthermore, CYP4F2 overexpression repressed the expression of genes in the nuclear factor, erythroid 2 like 2 (Nrf2) signaling pathway, including Nrf2, heme oxygenase-1 and ferritin heavy chain 1, while increasing NAD(P)H quinone dehydrogenase 1 expression, suggesting that CYP4F2 overexpression reversed the antioxidant response of liver cancer cells. Overall, the present findings indicated that CYP4F2 may be a potential prognostic biomarker for predicting tumorigenesis and long-term survival rates in patients with HCC.