PSMB5 is significantly up-regulated in patients with bladder and urothelial carcinoma and may be associated with prognosis. However, the biological and immunological role of PSMB5 in bladder carcinoma remains to be determined.

We analyze the expression of PSMB5 via multiple gene expression databases and identify its genetic alterations and functional networks. We evaluated the influence of PSMB5 clinical prognosis using the UALCAN database and Gene Expression Profiling Interactive Analysis (GEPIA). Co-expressed genes with PSMB5 and their regulators were identified using LinkedOmics. The correlation between PSMB5 and cancer immunosuppression was investigated using TIMER. In addition, TIMER and GEPIA were used to analyze the correlation between PSMB5 expression and gene marker sets of immune infiltrators.

Significantly elevated transcriptional and proteomic PSMB5 expressions were found in the BC sample. Increased PSMB5 expression was significantly associated with decreased survival in TNM III-IV and correlated with shorter PFS and OS (p < 0.001). Functional annotations indicate that PSMB5 is involved in biological regulation, metabolic processes, response to stimuli and cell cycle signaling via pathways involving several cancer-related kinases and the E2F family. Notably, PSMB5 expression was positively correlated with levels of immune infiltrating CD8+T cells, macrophages and neutrophils.. PSMB5 expression is associated with the NRP1, STAT1 and GATA3 genes, which potentially activate dendritic cells and affect the Th1/ Th2 balance.

Our study has revealed that elevated PSMB5 expression is significantly associated with poor survival and immune infiltration in BC patients. These data suggest that PSMB5 may serve as a promising prognostic and immunological marker in BC.