Integrative multi-omics analysis identifies AEBP1 and EFEMP2 as key regulators of immune heterogeneity and therapeutic response in glioblastoma.

OBJECTIVE: Glioblastoma (GBM) is a highly aggressive brain tumor with complex immune microenvironment and molecular heterogeneity. This study aimed to characterize immune infiltration patterns and identify prognostic biomarkers in GBM. METHODS: We classified GBM samples using immune-related gene sets and correlated subtypes with molecular features. Key genes were identified through Cox and LASSO regression analyses. Multi-omics approaches including single-cell RNA sequencing, transcriptional network analysis, and molecular docking were employed to investigate therapeutic targets. RESULTS: Two immune subtypes (c1/c2) were identified, with c2 showing mesenchymal features and poorer prognosis. Four immune-related genes (RPL39L, AEBP1, EFEMP2, GALNT12) were prognostic markers, with AEBP1 and EFEMP2 overexpressed in GBM. Single-cell analysis revealed five tumor subtypes, with MES-like being most malignant. NFIA and BATF3 were key regulators. Seven potential drugs (e.g., Bosutinib) were identified with stable target binding. CONCLUSIONS: This study reveals immune-molecular interactions in GBM, identifies AEBP1/EFEMP2 as prognostic markers, and proposes targeted therapies for personalized treatment.