Gut Liver.  2016 Sep;10(5):826-835. 10.5009/gnl15543.

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

• Ha SY
• Paik YH
• Yang JW
• Lee MJ
• Bae H
• Park CK

• KMID: 2412082
• DOI: http://doi.org/10.5009/gnl15543

Abstract

BACKGROUND/AIMS
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.
METHODS
NOX1 and NOX4 protein expression was examined by using immunohistochemistry in tumor tissue from 227 HCC patients who underwent hepatectomy.
RESULTS
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.
CONCLUSIONS
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.

Keyword

NOX1; NOX4; Carcinoma; hepatocellular; Prognosis

MeSH Terms

Adolescent
Adult
Aged
Biomarkers, Tumor/analysis
Carcinoma, Hepatocellular/*enzymology/pathology/surgery
Disease-Free Survival
Female
*Hepatectomy
Humans
Immunohistochemistry
Liver Neoplasms/*enzymology/pathology/surgery
Male
Middle Aged
NADPH Oxidase 1
NADPH Oxidase 4
NADPH Oxidases/*analysis
Neoplasm Staging
Postoperative Period
Prognosis
Tumor Burden
Young Adult
alpha-Fetoproteins/analysis
Biomarkers, Tumor
alpha-Fetoproteins
NADPH Oxidase 1
NADPH Oxidase 4
NADPH Oxidases