Association of HPGDS Expression with Prognosis and Immune Microenvironment Remodeling in Pancreatic Cancer

Abstract

Background Pancreatic ductal adenocarcinoma (PAAD) is a highly lethal malignancy characterized by metabolic remodeling and an immunosuppressive tumor microenvironment. Hematopoietic prostaglandin D synthase (HPGDS), a key enzyme involved in prostaglandin and lipid-associated inflammatory signaling, remains insufficiently characterized in PAAD. Methods We integrated public transcriptomic datasets, survival cohorts, immunotherapy-related datasets, single-cell RNA sequencing data, and in vitro validation assays to evaluate the expression pattern, clinical relevance, immune association, and functional role of HPGDS in pancreatic cancer. Results HPGDS was upregulated in pancreatic cancer tissues and cell lines and was associated with clinicopathological progression and unfavorable prognosis. HPGDS expression correlated with immune checkpoint molecules, immune cell infiltration, chemokine receptor networks, and cell-cell communication programs within the pancreatic tumor microenvironment. In public immunotherapy cohorts, higher HPGDS expression was associated with poorer response to immune checkpoint blockade, although the predictive performance varied across cohorts. Pharmacological inhibition and shRNA-mediated knockdown supported a role for HPGDS in pancreatic cancer cell proliferation, whereas effects on migration and invasion were less consistent between inhibitor-based and genetic approaches. Conclusion These findings suggest that HPGDS is associated with prognosis and immune microenvironment remodeling in pancreatic cancer and may represent a candidate biomarker for further translational investigation. Because many findings are based on retrospective public datasets and correlation analyses, additional mechanistic, in vivo, and clinical validation studies are required.