MET-associated immune prognostic signature predicts survival and guides personalized therapy in glioma.

Glioma is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment (TME) that drives therapeutic resistance. MET alterations promote tumor progression and immune evasion, yet their clinical implications in glioma immunotherapy remain unclear. Here, we integrated multi-omics data from four independent cohorts to establish a MET-associated immune prognostic signature (MIPS) comprising 18 immune-related genes. MIPS effectively stratified glioma patients into low- and high-MIPS subgroups. High-MIPS patients exhibited significantly poorer overall survival than low-MIPS patients across all cohorts and was an independent prognostic factor independent of clinicopathological and molecular features. High-MIPS scores correlated with increased M2 macrophage infiltration, elevated B7-H3 expression, and higher TIDE scores, indicating immunotherapy resistance. Bioinformatic prediction and patient-derived organoid assays verified that low-MIPS tumors were sensitive to multiple targeted drugs (e.g., Axitinib, AZD-8055, Gefitinib, and Lenalidomide), while high-MIPS tumors were relatively resistant. MIPS derived from MET alteration serves as a robust biomarker for prognosis and predictive tool for immunotherapy and chemotherapy, facilitating patient stratification and precision therapy.