NDUFB2, HSP90B1, and LITAF in Astrocytes Can Serve as Key Indicators for Overall Survival in Glioblastoma Patients

<title>Abstract</title> <p>Objective To explore astrocyte molecular signatures, intercellular communication, and prognostic relevance in glioblastoma (GBM), and to elucidate their immune microenvironment modulation. Methods Single‑cell RNA‑seq was performed on tumor and adjacent normal tissues from 3 GBM patients, integrated with public spatial transcriptomics (GSE253080) for deconvolution and cell–cell communication. Differential expression and GO/KEGG enrichment characterized astrocyte functional changes. TCGA transcriptomic data were used for WGCNA, LASSO Cox, and univariate Cox regression to screen prognostic genes, with CIBERSORT assessing immune infiltration correlations. Results Nine major cell types were identified; astrocytes and microglia were significantly elevated in GBM. Spatial transcriptomics confirmed astrocytes as dominant, with strong signaling crosstalk with microglia. Upregulated DEGs enriched in ribosomal, oxidative phosphorylation, and neurodegeneration pathways; downregulated DEGs in extracellular matrix and adhesion. WGCNA identified pink and red modules positively correlated with GBM. Machine learning and Cox regression identified NDUFB2, HSP90B1, and LITAF as independent prognostic risk factors (all P &lt; 0.001); the risk score stratified patients into high‑ and low‑risk groups. NDUFB2 correlated positively with CD8⁺ T and γδT cells; HSP90B1 with Tregs and M2 macrophages; LITAF with CD4⁺ activated T cells but negatively with follicular helper T cells. Conclusions Astrocytes in GBM exhibit bidirectional remodeling—“metabolic activation versus matrix‑interaction suppression.” NDUFB2, HSP90B1, and LITAF are independent prognostic biomarkers and may reshape the immune microenvironment through differential immune cell regulation, offering novel insights for GBM targeted therapy and prognosis.</p>