Abstract
Metabolic reprogramming is an established hallmark of multiple cancers, including pancreatic cancer. Dysregulated metabolism is utilized by cancer cells for tumor progression, metastasis, immune microenvironment remodeling, and therapeutic resistance. Prostaglandin metabolites have been shown to be critical for inflammation and tumorigenesis. While the functional role of prostaglandin E2 metabolite has been extensively studied, there is a limited understanding of the PTGES enzyme in pancreatic cancer. Here, we investigated the relationship between expression of prostaglandin E synthase (PTGES) isoforms and the pathogenesis and regulation of pancreatic cancer. Our analysis identified higher expression of PTGES in pancreatic tumors compared to normal pancreatic tissues, suggesting an oncogenic function. Only PTGES1 expression was significantly correlated with worse prognosis of pancreatic cancer patients. Further, utilizing cancer genome atlas data, PTGES was found to be positively correlated with epithelial-mesenchymal transition, metabolic pathways, mucin oncogenic proteins, and immune pathways in cancer cells. PTGES expression was also correlated with higher mutational burden in key driver genes, such as TP53 and KRAS. Furthermore, our analysis indicated that the oncogenic pathway controlled by PTGES1 could be regulated via DNA methylation-dependent epigenetic mechanisms. Notably, the glycolysis pathway was positively correlated with PTGES and may fuel cancer cell growth. PTGES expression was also associated with downregulation of the MHC pathway and negatively correlated with CD8+ T cell activation markers. In summary, our study established an association of PTGES expression with pancreatic cancer metabolism and the immune microenvironment.