Abstract
BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a highly aggressive cancer with poor prognosis and limited therapeutic options. Identifying molecular markers and understanding their role in PAAD pathogenesis is crucial for developing targeted therapies. This study integrates bioinformatics and molecular experiments to investigate the diagnostic, prognostic, and therapeutic significance of FGFBP1 in PAAD. METHODS: UALCAN, TNMplot, OncoDB, GEPIA2, HPA, GSCA, KM Plotter, TISIDB, TISCH2, CancerSEA, STRING, DAVID, cell culture, RT-qPCR analysis, western blot analysis, colony formation, cell proliferation, and wound healing assays. RESULTS: Expression analyses revealed a significantly elevated FGFBP1 levels in PAAD tissues compared to normal samples. Promoter methylation analysis indicated lower methylation levels in PAAD, inversely correlated with FGFBP1 expression, suggesting epigenetic regulation. Genetic alteration analysis showed that FGFBP1 is not significantly affected by single nucleotide variants, but copy number variations are present without impacting mRNA expression. Survival analysis using KM plotter demonstrated that high FGFBP1 expression is associated with poor overall and disease-free survival. A Cox regression-based prognostic model confirmed the negative impact of elevated FGFBP1 on patient outcomes. Correlation analysis with immune-related factors indicated that FGFBP1 may contribute to an immunosuppressive tumor microenvironment, affecting immune cell infiltration and function. Single-cell analysis highlighted FGFBP1 expression in malignant, endothelial, and fibroblast cells within the tumor microenvironment. Gene enrichment analysis revealed FGFBP1's involvement in various biological processes and pathways related to cancer progression. Experimental validation using RT-qPCR confirmed high FGFBP1 expression in PAAD cell lines. FGFBP1 knockdown in HEK293T cells significantly reduced cell proliferation, colony formation, and migration. CONCLUSION: These findings suggest that FGFBP1 plays a critical role in PAAD pathogenesis and could serve as a potential therapeutic target for improving patient outcomes.