Potential of APOBEC3B as a therapeutic target and its role in bladder cancer onset and progression

Background: This study aims to investigate the impact of apolipoprotein B mRNA editing enzyme catalytic polypeptide 3B (APOBEC3B/A3B) on the malignant biological characteristics of bladder cancer (BCa). Additionally, the study examines the potential mechanisms of A3B’s action to assess its feasibility as a therapeutic strategy for BCa. Methods: The study first confirmed A3B expression in BCa using bioinformatics and experi- mental validation. Then, the relationship between A3B expression and various parameters was analyzed, with gene set enrichment analysis to explore pathways. The IMvigor210 cohort was analyzed to validate the correlation between A3B expression and immunotherapy efficacy. Results: Cellular and animal experiments further validated the impact of A3B on BCa biology. The BCa patients with high A3B expression exhibit an increased frequency of somatic mutations. A3B expression levels are significantly correlated with the infiltration of various immune cells and the expression of immune checkpoint-related genes. Moreover, high A3B expression is associated with increased tumor mutation burden. In the IMvigor210 cohort, A3B expression is significantly upregulated in individuals with positive responses to immunotherapy. Our study suggests that A3B plays a key role in promoting the initiation and progression of BCa. Additionally, BCa cells with overexpressed A3B can enhance the polarization of M2-like tumor-associated macrophages. Conclusion: The research demonstrates that A3B exhibits high expression levels in BCa and can enhance its malignant biological behavior. Therefore, A3B may serve as a promising therapeutic target in future treatments.