RAD54B as a biomarker for prognosis and immunotherapy response in bladder cancer.

[BACKGROUND] RAD54B is a homologous recombination–related DNA repair protein involved in maintaining genomic stability. However, its expression profile, clinical relevance, and immunological role in bladder cancer remain unclear. This study systematically explored the clinical significance of RAD54B in bladder cancer.

[METHODS] We conducted a comprehensive, multi-cohort analysis to evaluate the clinical significance of RAD54B in bladder cancer. RAD54B expression was evaluated using paired and unpaired analyses, promoter methylation profiling, single-cell RNA sequencing, and data from bladder cancer cell lines. Tumor immune infiltration was estimated using CIBERSORT, and immunotherapy response was predicted using immunophenoscore (IPS). RAD54B protein expression was validated by immunohistochemistry in a bladder cancer tissue microarray.

[RESULTS] RAD54B was significantly upregulated in bladder cancer and multiple malignancies and was associated with promoter hypomethylation. Higher levels of RAD54B were associated with significantly improved patient outcomes across multiple independent cohorts. Functional enrichment analyses revealed that RAD54B was primarily involved in DNA damage repair, cell cycle regulation, RNA metabolism, and genomic stability, while immune-related pathways were relatively suppressed. High RAD54B expression was linked to elevated memory B cells, naïve CD4⁺ T cells, and activated dendritic cells, while low expression was associated with increased activated memory CD4⁺ T cells, M2 macrophages, and neutrophils. Notably, patients with low RAD54B expression exhibited higher IPS scores under PD-1– and CTLA4–positive conditions, suggesting enhanced sensitivity to immune checkpoint blockade.

[CONCLUSIONS] RAD54B serves as both a prognostic biomarker and an immune modulator in bladder cancer, supporting its use in immunotherapeutic stratification.