Potential impact of epithelial splicing regulatory protein 1 (ESRP1) associated with tumor immunity in pancreatic adenocarcinoma.

ABSTRACT

Pancreatic adenocarcinoma (PAAD) is a prevalent and highly malignant gastrointestinal tumor. Therefore, exploring the mechanisms of drug resistance and immune pathways in PAAD is crucial for clinical treatment. In this study, a total of 497 differentially expressed genes (DEGs) were identified between normal and PAAD samples, and which were enriched to 117 GO terms and 7 functional pathways. Subsequently, 5 overall survival-related DEGs (ESRP1, KRT6A, H2BC11, H2BC4 and KLK) was generated using Cox hazards regression analysis in TCGA dataset. Furthermore, the weighted gene co-expression network analysis revealed a strong association between ESRP1 and PAAD among 5 survival-related DEGs. Patients were divided into two clusters based on ESRP1 expression levels, and low ESRP1 expression existed stronger immune infiltration and higher expression of immunomodulatory targets than high ESRP1 expression by single-sample gene set enrichment analysis, which indicated that low ESRP1 expression was associated with longer survival compared to high ESRP1 expression. Finally, our study also found that immune cells distribution and immunomodulatory targets gene expression in the GEO dataset were similar to the TCGA cohort. Overall, our findings suggest that ESRP1 may play a role in influencing immune contexture and regulating immune function of PAAD patients by integrating data from various databases. SIGNIFICANCE: Utilizing TCGA and GEO datasets, this study uncovers the significant impact of epithelial splicing regulatory protein 1 (ESRP1) on PAAD. ESRP1 emerges as a key regulator of immune function, influencing tumor microenvironment and immune cell infiltration. Cluster analysis shows that low ESRP1 expression correlates with enhanced immune activity, predicting better prognosis. This discovery suggests that ESRP1 can serve as a potential biomarker for the prognosis of PAAD, offering new insights into personalized immunotherapy by influencing immune regulation and tumor progression.