TRPM4 expression predicts prognosis and modulates the immune microenvironment in pancreatic adenocarcinoma

TRPM4, a nonselective cation channel, has been implicated in a variety of tumorigenic processes and is closely linked to insulin secretion. However, its functions and underlying mechanisms in pancreatic ductal adenocarcinoma (PAAD) progress remain elusive, and the potential as PAAD biomarker and therapeutic target remains unexplored. This study was meticulously crafted to experimentally validate the expression of TRPM4 in PAAD and to undertake a thorough examination of its effects on expression patterns, prognostic significance, mutational landscapes, methylation statuses, protein-protein interaction networks, as well as the correlation between TRPM4 expression and immune infiltration in PAAD. Our analytical approach included KEGG pathway analysis and GO enrichment analysis to identify signaling pathways associated with TRPM4. Our findings reveal a significant overexpression of TRPM4 in PAAD tissues, with heightened expression levels tightly correlated with unfavorable clinical outcomes. A comprehensive analysis utilizing the cBioPortal database unveiled a high mutation rate of TRPM4 in pancreatic cancer, predominantly attributed to gene amplification events. Examination of PPI networks and co-expression gene profiles highlighted notable interactions between TRPM4 and crucial ion channel proteins, including voltage-gated sodium channels and calcium release-activated calcium channels, shedding light on its potential role in PAAD progression. Functional enrichment analysis implicated TRPM4 in a range of biological processes, encompassing immune responses, neural signaling, and cellular electrophysiology, with particular emphasis on endocrine system regulation, especially pancreatic hormone secretion. Furthermore, TRPM4 expression exhibited striking associations with infiltration patterns of diverse immune cell populations in PAAD, particularly demonstrating strong correlations with Th17 cells and iTregs, hinting at its potential regulatory role in the tumor immune microenvironment. TRPM4 demonstrates heightened expression in pancreatic cancer tissues relative to normal tissues. It is also linked to the prognosis of pancreatic cancer patients, the intratumoral immune microenvironment, and the dissemination of the disease. These findings imply a potential oncogenic role for TRPM4. Moreover, TRPM4 potentially interacts with other ion channels, including sodium and calcium channels, to regulate the behavior of pancreatic cancer cells.