Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGF-Related Phenotype: An Exploratory Analysis

Background: Over the past few decades, there has been much debate and research into the link between alcohol consumption and the development and progression of pancreatic ductal adenocarcinoma (PDAC). Objectives: To contribute to the ongoing discussion and gain further insights into this topic, our study analysed the gene expression differences in PDAC patients based on their alcohol consumption history. Methods: To this end, we interrogated a large publicly available dataset. We next validated our findings in vitro. Results: Our findings revealed that patients with a history of alcohol consumption showed significant enrichment in the TGF beta-pathway: a signaling pathway implicated in cancer development and tumor progression. Specifically, our bioinformatic dissection of gene expression differences in 171 patients with PDAC showed that those who had consumed alcohol had higher levels of TGF beta-related genes. Moreover, we validated the role of the TGF beta pathway as one of the molecular drivers in producing massive stroma, a hallmark feature of PDAC, in patients with a history of alcohol consumption. This suggests that inhibition of the TGF beta pathway could serve as a novel therapeutic target for PDAC patients with a history of alcohol consumption and lead to increased sensitivity to chemotherapy. Our study provides valuable insights into the molecular mechanisms underlying the link between alcohol consumption and PDAC progression. Conclusions: Our findings highlight the potential significance of the TGF beta pathway as a therapeutic target. The development of TGF beta-inhibitors may pave the way for developing more effective treatment strategies for PDAC patients with a history of alcohol consumption.