Multidimensional analysis of the prognostic impact of PSMB2 in pancreatic ductal adenocarcinoma via the ECM-receptor interaction pathway

Abstract:

Background and Aims Proteasome 20S subunit β2 (PSMB2) has been implicated in tumor progression in multiple cancers; however, its expression pattern, prognostic value, and underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study aimed to investigate the clinical significance and potential mechanisms of PSMB2 in PDAC through integrated bioinformatics analysis and clinical validation.Methods Expression profiles and clinical data from TCGA and GEO datasets (GSE62452 and GSE15471) were analyzed to evaluate PSMB2 expression and its prognostic significance. Kaplan-Meier survival analysis and Cox regression models were used. Immunohistochemistry was performed on 76 PDAC samples for validation. Gene Set Enrichment Analysis (GSEA) and correlation analyses were conducted to explore potential mechanisms. Immune cell infiltration was assessed using ssGSEA, and immunotherapy response was predicted using TCIA data. Drug sensitivity was analyzed based on the GDSC database.Results IPSMB2 expression was significantly upregulated in PDAC tissues, and high expression was associated with poorer overall survival (all P<0.05). Multivariate Cox analysis identified PSMB2 as an independent prognostic factor. Immunohistochemical results were consistent with bioinformatics findings. PSMB2 expression correlated with lymph node metastasis, pathological stage, and differentiation. GSEA indicated enrichment in the ECM-receptor interaction pathway. Correlation analysis showed positive associations with multiple ECM-related genes. Additionally, PSMB2 was associated with immune cell infiltration and predicted immunotherapy response. Higher PSMB2 expression was also linked to increased sensitivity to several targeted agents.Conclusion PSMB2 is overexpressed in PDAC and is associated with poor prognosis, serving as an independent prognostic biomarker. Its role may involve regulation of the ECM-receptor interaction pathway and tumor immune microenvironment, highlighting its potential as a therapeutic target.