Cytochrome P450 4A11 expression in tumor cells: A favorable prognostic factor for hepatocellular carcinoma patients.
Hyuk Soo Eun, Sang Yeon Cho, Byung Seok Lee, Sup Kim, In-Sang Song, Kwangsik Chun, Cheong-Hae Oh, Min-Kyung Yeo, Seok Hyun Kim, Kyung-Hee Kim
Author Information
Hyuk Soo Eun: Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea. ORCID
Sang Yeon Cho: College of Medicine, Chungnam National University School of Medicine, Daejeon, Korea.
Byung Seok Lee: Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea.
Sup Kim: Department of Microbiology, Infection Control Convergence Research Center, Medical Science, Radiation Oncology, Chungnam National University School of Medicine, Daejeon, Korea.
In-Sang Song: Department of Surgery, Chungnam National University Hospital, Daejeon, Korea.
Kwangsik Chun: Department of Surgery, Chungnam National University Hospital, Daejeon, Korea.
Cheong-Hae Oh: Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea.
Min-Kyung Yeo: Department of Pathology, Chungnam National University School of Medicine, Daejeon, Korea.
Seok Hyun Kim: Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea.
Kyung-Hee Kim: Department of Pathology, Chungnam National University School of Medicine, Daejeon, Korea. ORCID
BACKGROUND AND AIM: Elevated cytochrome p450 (CYP) 4A gene expression has been linked to the aggravation of various cancers and affects various regulated metabolites. In hepatocellular carcinoma (HCC), the clinicopathological value of CYP4A has not yet been explored, although CYP4A is expressed at high levels in the liver. The goal of this study was to evaluate the clinicopathological value of CYP4A11 expression in HCC. METHODS: We performed immunohistochemical analysis of CYP4A11 and correlated the results with clinicopathological features of HCC (n = 155). Western blotting and reverse transcription-polymerase chain reaction against CYP4A11 and CYP4A22 were also performed for 15 and 20 pairs of fresh-frozen primary HCC and non-neoplastic liver tissue, respectively. Moreover, we analyzed the underlying mechanism by comparing the high and low CYP4A11 mRNA expression groups using gene set enrichment analysis. RESULTS: CYP4A11 expression level was higher in non-neoplastic hepatocytes than those in HCC cells (P < 0.001), and CYP4A11 expression positively correlated with favorable prognostic factors, including tumor size, histological grade, and pathological tumor stage (P = 0.007, P = 0.005, and P = 0.007). Multivariate analysis revealed that CYP4A11 expression was an independent prognostic factor of overall and disease-free survival (P = 0.002 and P = 0.033). Based on gene set enrichment analysis, high CYP4A11 mRNA expression negatively correlated with the expression of cell cycle-related genes. CONCLUSION: These findings support the notion that CYP4A11 expression is a favorable prognostic factor of HCC and suggest potential predictive diagnostic and prognostic roles of CYP4A11 expression in HCC.
