Identification of alcohol dehydrogenase as a potential prognostic marker in HBV-related hepatocellular carcinoma

Objective: Studies have shown that alcohol dehydrogenase (ADH) expression is associated with cancer risk. This study investigated the prognostic value of ADH gene expression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Materials and methods: Microarray analysis and survival profiles of HBV-related HCC from GSE14520 were used to assess the association between ADH gene expression and patient outcome. Statistical correlations between ADH gene expression profiles and predefined gene signatures were investigated by gene set enrichment analysis (GSEA). Results: A total of 218 HBV-related HCC patients and six ADH genes were examined. ADH mRNA expression level was markedly reduced in HBV-related HCC tumor tissue. ADH1C and ADH5 overexpression in tumor tissue was significantly decreased the risk of tumor recurrence [adjusted P = 0.005, adjusted hazard ratio (HR) = 0.581, 95% confidence interval (CI) = 0.398-0.848 and adjusted P = 0.025, adjusted HR = 0.658, 95% CI = 0.455-0.950, respectively], whereas ADH1A, ADH1C, and ADH6 overexpression was associated with decreased risk of cancer-related death in HBV-related HCC patients (adjusted P = 0.035, adjusted HR = 0.614, 95% CI = 0.389-0.967; adjusted P = 0.024, adjusted HR = 0.588, 95% CI = 0.371-0.933; and adjusted P = 0.001, adjusted HR = 0.449, 95% CI = 0.282-0.715; respectively). GSEA showed that ADH1A and ADH6 were significantly related to liver cancer survival, whereas ADH1C was significantly associated with liver cancer. Conclusions: Upregulation of ADH genes (ADH1A, ADH1C, ADH5, and ADH6) may have protective effects in HBV-related HCC patients after hepatectomy. Our findings suggest that these genes are potential prognostic markers for HBV-related HCC patients.