Pancreatic ductal adenocarcinoma with a high expression of alcohol dehydrogenase 1B is associated with less aggressive features and a favorable prognosis.

Alcohol dehydrogenase (ADH) oxidizes alcohol into acetaldehyde (AA), which is a known carcinogen. Aldehyde dehydrogenase (ALDH) oxidizes AA into acetate. Therefore, pancreatic cancer that expresses a high level of ADH1B that generates more AA is expected to be associated with aggressive cancer. On the other hand, given that the differentiated cells that retain their cellular functions typically exhibit lower proliferation rates, it remains unclear whether pancreatic adenocarcinoma (PDAC) with high gene expression is linked to aggressive features in patients. The Cancer Genome Atlas ( = 145) was used to obtain data of PDAC patients and GSE62452 cohort ( = 69) was used as a validation cohort. PDAC with high expression was associated with less cancer cell proliferation as evidenced by lower expression and lower histological grade; with a higher fraction of stromal cells consistent with less proliferative cancer. PDAC with high expression also had lower homologous recombination deficiency and mutation rates, lower and mutation rates. expression correlated with expression in PDAC, but not with DNA repair genes. High expression PDAC was associated with high infiltration of anti-cancerous CD8 T cells and pro-cancerous M2 macrophages but with lower levels of Th1 T cells, with a higher cytolytic activity. PDAC patients with a high expression had better disease-specific survival (DSS) and overall survival (OS) and was an independent prognostic biomarker for both DSS (HR = 0.89, 95% CI = 0.80-0.99, = 0.045) and OS (HR = 0.90, 95% CI = 0.82-0.99, = 0.044) in multivariate analysis. In conclusion, PDAC with high expression had less cell proliferation and malignant features, along with higher immune cell infiltration, and had a better prognosis.