Xiwen Liao, Rui Huang, Xiaoguang Liu, Chuangye Han, Long Yu, Shijun Wang, Na Sun, Bopei Li, Xin Ning, Tao Peng

Alcohol dehydrogenase (ADH) isoenzymes have been reported as a potential diagnostic marker for pancreatic cancer, but their prognostic value in pancreatic cancer remains unclear. The aim of this investigation was to identify the prognostic value of ADH genes in human patients with pancreatic adenocarcinoma (PAAD). An RNA sequencing dataset and corresponding survival profiles of PAAD were obtained from The Cancer Genome Atlas. Survival analysis and gene set enrichment analysis were used to investigate the prediction value and potential mechanism of ADH genes in PAAD prognosis. Survival analysis of ADH genes suggests that a high expression of ADH1A (adjusted P=0.037, adjusted hazard ratio [HR] =0.627, 95% CI =0.404-0.972) and ADH6 (adjusted P=0.018, adjusted HR =0.588, 95% CI =0.378-0.914) were associated with a significantly decreased risk of death, while a high expression of ADH5 was associated with a significantly increased risk of death (adjusted P=0.043, adjusted HR =1.564, 95% CI =1.013-2.414). Joint effects analysis of three ADH gene prognostic markers suggests that the prognosis difference for any marker combination was more significant than that for any individual marker. The potential mechanism of ADH1A and ADH6 in PAAD prognosis was that a high expression of ADH1A and ADH6 was involved in the P450 pathway and biological processes, while high ADH5 expression was involved in transforming growth factor β regulation-related pathways and biological processes, Wnt, the cell cycle, ErbB, and mitogen-activated protein kinase signaling pathways. Our data suggest that ADH1A, ADH5, and ADH6 expression may be potential prognostic markers of PAAD and in combination have a strong interaction and better predictive value for PAAD prognosis.