Gene expression of NOX family members and their clinical significance in hepatocellular carcinoma

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex-derived reactive oxygen species (ROS) promote chronic liver inflammation and remodeling that can drive hepatocellular carcinoma development. The role of NOX expression in hepatocellular carcinoma (HCC) has been partially investigated; however, the clinical relevance of collective or individual NOX family member expression for HCC survival remains unclear. Here, we obtained NOX mRNA expression data for 377 HCC samples and 21 normal liver controls from the TCGA data portal and performed Kaplan-Meier survival, gene ontology functional enrichment, and gene set enrichment analyses. Although most NOX genes exhibited little change, some were significantly induced in HCC compared to that in normal controls. In addition, HCC survival analyses indicated better overall survival in patients with high NOX4 and DUOX1 expression, whereas patients with high NOX1/2/5 expression showed poor prognoses. Gene-neighbour and gene set enrichment analyses revealed that NOX1/2/5 were strongly correlated with genes associated with cancer cell survival and metastasis, whereas increased NOX4 and DUOX1 expression was associated with genes that inhibit tumour progression. On the basis of these data, NOX family gene expression analysis could be a predictor of survival and identify putative therapeutic targets in HCC.