Targeted redox gene-expression profiling reveals shared and distinct expression patterns in HBV- and HCV-associated hepatocellular carcinoma.

BACKGROUND

Oxidative stress and redox dysregulation are important features of hepatocellular carcinoma (HCC), but their expression patterns in hepatitis B virus (HBV)- and hepatitis C virus (HCV)-associated HCC remain incompletely characterized. This study investigated redox-related gene expression and its potential functional and prognostic relevance.

METHODS

A predefined 84-gene oxidative stress and redox-related quantitative real-time PCR array was used to profile 11 HCC samples (7 HCV-associated and 4 HBV-associated tumors) and 4 controls. Analyses included hierarchical clustering, gene-list overlap, functional enrichment, protein-protein interaction networks, gene-expression correlations, and exploratory survival analysis.

RESULTS

Both HCC groups exhibited altered expression of genes associated with antioxidant defense, glutathione metabolism, mitochondrial redox regulation, and ferroptosis-related processes. In HCV-associated HCC versus controls, TXN, SPINK1, HSP90AA1, and DUSP1 showed increased expression. In HBV-associated HCC versus controls, GCLC, peroxiredoxins, CAT, and SOD1 showed increased expression. Eighteen genes were shared between comparison lists, including GPX4, GPX2, GPX3, PRDX1, PRDX5, TXN, GCLM, SOD2, and FTH1. Enrichment analyses implicated glutathione metabolism, oxidative stress, peroxisome function, and ferroptosis-associated processes. Network analysis identified GPX2, GPX3, GPX4, and SOD2 in a connected module. External exploratory survival analysis associated higher SPINK1 and HSP90AA1 expression with poorer overall survival.

CONCLUSIONS

These findings identify redox-related expression patterns warranting further investigation. Larger cohorts and functional studies are needed to establish etiological differences, ferroptosis susceptibility, and prognostic significance.