Integrative In Silico Transcriptomic and Pharmacogenomic Analysis of CD276 as a Candidate Prognostic Biomarker and Therapeutic Target in Bladder Cancer

Despite recent advances in bladder cancer treatment, therapeutic resistance remains a critical challenge, necessitating the identification of novel molecular targets. This study used an integrative in silico approach to evaluate the prognostic value and molecular landscape of the immune regulatory molecule CD276 (B7-H3). Analyses of TCGA and GTEx datasets showed that CD276 is significantly upregulated in tumor tissues compared with normal controls, with higher expression in Stage 2 and beyond relative to normal and Stage 1. Kaplan Meier and univariate Cox regression analyses indicated that high CD276 expression is associated with poorer overall survival. Mechanistically, CD276 expression was associated with PI3K–Akt pathway enrichment and a myeloid/macrophage enriched immune contexture, including M2 like macrophage signatures. Finally, pancancer pharmacogenomic profiling across large cancer cell line panels suggested a broad resistance-associated pattern in CD276 high models, with reduced sensitivity (higher IC50) to PI3K/mTOR inhibitors and several cytotoxic agents used in urothelial cancer regimens (e.g., gemcitabine and methotrexate). Collectively, these findings support CD276 as a candidate biomarker linked to aggressive biology and motivate experimental and clinical validation of CD276 directed strategies in advanced bladder cancer.