CD276 (B7-H3) as a Companion Diagnostic Biomarker for Glioblastoma: Multi-Platform Validation and Therapeutic Implications

Abstract Glioblastoma (GBM) remains the most lethal primary brain tumor, with median survival of 14-16 months despite aggressive multimodal therapy [1,2] . The failure of PD-1/PD-L1 checkpoint inhibitors in GBM (CheckMate-143) [3] has highlighted the need for alternative immunotherapeutic targets and companion diagnostics. CD276 (B7-H3) has emerged as a promising target, with multiple anti-B7-H3 therapies in clinical development including monoclonal antibodies, antibody-drug conjugates (ADCs), and CAR-T cells [4-6] . However, no validated companion diagnostic exists to stratify patients for these therapies. Here we present comprehensive validation of CD276 as a prognostic biomarker in GBM across multiple independent platforms. Using discovery analysis in TCGA (n=154) and independent validation in CPTAC proteomics (n=99) [7] , we demonstrate that CD276-high expression is associated with significantly shorter survival (Δ=3.5-4.0 months, p=0.003-0.013). RNA expression correlates strongly with protein (r=0.75, p