Integrated analysis implicates novel insights of NMB into lactate metabolism and immune response prediction in primary glioblastoma

Abstract

BackgroundGlioblastoma (GBM), the most aggressive primary brain tumor in adults, exhibits profound treatment resistance and poor prognosis. Despite advances in immunotherapy for other cancers, GBM remains refractory, potentially due to its lactate-rich, immunosuppressive tumor microenvironment (TME). While aerobic glycolysis-driven lactate accumulation is known to acidify the TME and impair immune function, the precise mechanisms linking lactate metabolism to immune evasion in GBM remain elusive. MethodsWe integrated multi-omics analyses with machine learning to identify - gene signatures associated lactate metabolism (LM) and Tumor Immune Dysfunction and Exclusion (TIDE) through weighted gene co-expression network analysis (WGCNA). Multiple bioinformatic tools were employed to determine the association of key genes with TME remodeling, immunotherapy response and drug sensitivities. ResultsNeuromedin B (NMB) emerged as a pivotal regulator of lactate-mediated immunosuppression, correlating strongly with LM and TIDE. We found that NMB expression was remarkably correlated with clinical characteristics, immune response, TME remodeling and drug sensitivities. ConclusionThis study demonstrates that NMB is a key cross-factor in metabolic and immune regulation in GBM. It breaks through the traditional perception that metabolism and immunity are mutually exclusive in cancer by promoting oxidative phosphorylation (OXPHOS) metabolism and enhancing anti-tumor immunity through its dual functions. It provides a new direction for the combined intervention of metabolic targeting and immunotherapy, and the strong predictive value of NMB expression for drug response further highlights its clinical application potential in the formulation of personalized treatment strategies for GBM patients.