GABRP is a potential prognostic biomarker and correlated with immune infiltration and tumor microenvironment in pancreatic cancer

BACKGROUND: Pancreatic cancer is one of the most commonly diagnosed and lethal malignancies worldwide and has few good biomarkers and therapeutic targets. GABRP is the π subunit of the gamma-aminobutyric acid (GABA) A receptor, which is expressed in a number of non-neuronal tissues. GABRP is significantly upregulated in pancreatic cancer, but its biological and immunological role as well as its clinical diagnostic and prognostic value in pancreatic cancer is still incompletely known. METHODS: In this study, pancreatic adenocarcinoma (PAAD) cohorts from TCGA and GEO datasets were used to compare GABRP mRNA levels in cancerous and normal tissues and protein expression was evaluated using immunohistochemistry. The Kaplan-Meier plotter and GEPIA2 database were used to analyze the correlation between GABRP expression, overall survival, and disease-free survival in pancreatic cancer patients. Gene set enrichment analysis (GSEA) was performed with the Linked Omics database to explore the molecular mechanisms of GABRP in pancreatic cancer. And the correlation between GABRP expression and immune infiltration was explored using the TIMER database, CIBERSORT database and ESTIMATE algorithm. RESULTS: GABRP mRNA was significantly overexpressed in TCGA-PAAD cohorts (P<0.0001) and enhanced GABRP expression predicted poorer overall survival according to Kaplan-Meier plotter database (P=0.0024) and GEPIA2 (P=0.038). Hypomethylation of promoter (P<0.01) and the regulation of hsa-miR-3655 may contribute to the overexpression of GABRP in pancreatic cancer. GSEA analysis revealed that GABRP played an important role in the immune response. GABRP expression was also correlated with immune infiltration and immune cell markers. Higher GABRP expression was significantly associated with greater infiltration of immune cells and stromal cells into pancreatic cancer microenvironments as well as higher expression of six important immune check point genes including PDCD1 (P<0.05), CD274 (P<0.05), CTLA4 (P<0.01), PDCD1LG2 (P<0.01), TIGHT (P<0.01) and TIM3 (P<0.01). CONCLUSIONS: GABRP is a potential prognostic biomarker and is correlated with immune infiltration and tumor microenvironment in pancreatic cancer. This suggests that GABRP may serve as a potential prognostic biomarker and therapeutic target in pancreatic cancer as well as a possible regulator of tumor microenvironment affecting the efficacy of immunotherapy. Further studies are needed to elucidate the molecular mechanism of the immunoregulatory role of GABRP.