Development and Validation of a Toxoplasma Infection-Associated Risk Model for Prognostic Stratification and Treatment Guidance in Glioma.

Gliomas are aggressive brain tumors with poor prognosis. The contribution of Toxoplasma gondii (T. gondii)-related transcriptional programs to glioma remains unclear. We identified T. gondii infection-related genes from neuroepithelial cell transcriptomes, mapped them to TCGA and CGGA glioma datasets, and validated their expression via RT-qPCR. A prognostic signature (TGRisk) was constructed via Cox and LASSO regression and validated across independent cohorts. Functional, immune, and drug sensitivity analyses were conducted. Forty infection-related genes were identified, enriched in stress responses, microRNA regulation, ribosome biogenesis, and metabolism. The 13-gene TGRisk model significantly separated survival between high- and low-risk groups. A nomogram combining TGRisk with clinical features improved prediction accuracy. High-risk tumors showed immune activation and higher infiltration of CD8+ T cells, Tregs, macrophages, and neutrophils, while low-risk tumors showed enhanced neuronal signaling and NK cell activity. Drug sensitivity prediction suggested low-risk patients were more responsive to temozolomide and bortezomib, whereas high-risk patients were more sensitive to dasatinib and ruxolitinib. We developed a novel T. gongdii infection-related gene signature that stratifies glioma patients by prognosis, immune features, and therapeutic vulnerabilities. These findings suggest host-T. gondii interactions and a potential biomarker for patient stratification and personalized therapy.