NADPH Oxidase 1 and NADPH Oxidase 4 Have Opposite Prognostic Effects for Patients with Hepatocellular Carcinoma after Hepatectomy

• Published in: Gut and liver Vol. 10; no. 5; pp. 826 - 835
• Main Authors: Ha, Sang Yun, Paik, Yong-Han, Yang, Jung Wook, Lee, Min Ju, Bae, Hyunsik, Park, Cheol-Keun
• Format: Journal Article
• Language: English
• Published: Korea (South) Editorial Office of Gut and Liver 01-09-2016; Gastroenterology Council for Gut and Liver; 거트앤리버 소화기연관학회협의회
• Subjects: Adolescent; Adult; Aged; alpha-Fetoproteins - analysis; Biomarkers, Tumor - analysis; carcinoma; Carcinoma, Hepatocellular - enzymology; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - surgery; Disease-Free Survival; Female; Hepatectomy; hepatocellular; Humans; Immunohistochemistry; Liver Neoplasms - enzymology; Liver Neoplasms - pathology; Liver Neoplasms - surgery; Male; Middle Aged; NADPH Oxidase 1; NADPH Oxidase 4; NADPH Oxidases - analysis; Neoplasm Staging; nox1; nox4; Original; Postoperative Period; Prognosis; Tumor Burden; Young Adult; 내과학; NOX4; Carcinoma; Prognosis; NOX1; hepatocellular
• ISSN: 1976-2283; 2005-1212
• DOI: 10.5009/gnl15543

Nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated reactive oxygen species contribute to various liver diseases, including hepatocellular carcinoma (HCC). Uncertainties remain regarding the prognostic relevance of NOX1 and NOX4 protein expression in HCC.
NOX1 and NOX4 protein expression was examined by using immunohistochemistry in tumor tissue from 227 HCC patients who underwent hepatectomy.
High immunoreactivity for NOX1 was observed in 197 (86.8%) of the 227 HCC cases and low immunoreactivity for NOX4 in 112 (49.3%). NOX1 and NOX4 proteins had opposite prognostic effects. High NOX1 expression was an independent predictor of both shorter recurrence-free survival (RFS) (p<0.01) and shorter overall survival (OS) (p=0.01). Low NOX4 expression was an independent predictor of both shorter RFS (p<0.01) and shorter OS (p=0.01). Subgroup analysis showed that, among patients with normal α-fetoprotein levels, patients with tumor size ≤5.0 cm and patients in Barcelona Clinic Liver Cancer stage A, high NOX1 expression had unfavorable effects on RFS, whereas low NOX4 expression had unfavorable effects on both RFS and OS.
These findings demonstrated that NOX1 and NOX4 protein expression had opposite prognostic effects for HCC patients. Moreover, both proteins had prognostic value in HCC patients with normal α-fetoprotein levels or with early-stage HCC.