The Role of PDGFRA in Predicting Oncological and Immune Characteristics in Pancreatic Ductal Adenocarcinoma.

Abstract

Objective Pancreatic ductal adenocarcinoma (PDAC) is a lethal solid gastrointestinal malignancy with poor immune infiltration and a limited response to immunotherapy. The aim of our study was to explore the predictive value of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs), which are widely expressed in various tumor cells. Methods Transcriptomic data with follow-up information were obtained from the GEO, TCGA and ArrayExpress. The Kaplan–Meier (KM) method and univariate Cox (UniCox) proportional hazard regression were used to show the survival outcomes of the groups. Immune infiltration was analyzed using the online databases TISCH, TISIDB, TIMER2.0, and TIDE as well as the R packages “estimate” and “GSVA.” Mutation and functional enrichment analyses were conducted using the R packages “maftools,” “clusterProfiler,” and online repository HOME for Researchers. Finally, the results were validated in 79 samples from our cancer center. Results Survival analysis using public databases and the FUSCC cohort indicated PDGFRA to be associated with prolonged overall survival (OS) (both p < 0.05). PDGFRA expression was highest in cancer-associated fibroblasts (CAFs) of PDAC, as validated in public databases and cell lines from our cancer center. The high expression of PDGFRA was associated with increased immune infiltration and potent T cell cytotoxicity in PDAC. Conclusion In summary, high PDGFRA expression is associated with increased immune infiltration and prolonged OS. This finding might provide a new strategy for regulating immune cell infiltration in PDAC and improving the efficacy of immunotherapy.