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 major clinical challenge, highlighting the need for novel molecular targets. In this study, we performed an integrative in silico analysis to evaluate the prognostic significance and molecular landscape of CD276 (B7-H3) in bladder cancer. Analyses of TCGA and GTEx datasets demonstrated significant upregulation of CD276 in tumor tissues compared with normal controls, with expression increasing across advanced clinical stages. Kaplan-Meier and univariate Cox regression analyses showed that high CD276 expression was associated with poorer overall survival. Functional enrichment analyses linked CD276 to PI3K-Akt signaling and a myeloid/macrophage-enriched immune microenvironment, including M2-like macrophage signatures. Pharmacogenomic analyses across large cancer cell line panels further suggested a resistance-associated phenotype in CD276 high models including reduced sensitivity to PI3K/mTOR inhibitors and several cytotoxic agents used in urothelial cancer treatment. Collectively, these findings support CD276 as a promising biomarker associated with aggressive biology and provide a rationale for future experimental and clinical validation of CD276 directed therapeutic strategies in advanced bladder cancer.