Toxoplasma gondii Seropositivity Correlates with High-Grade Gliomas and Aggressive Molecular Profiles: Implications for Prognostic Stratification in Precision Oncology

Abstract Purpose Chronic Toxoplasma gondii infection may enhance glioma malignancy through EGFR pathway activation. This study evaluates whether T. gondii seropositivity is associated with higher glioma grades and molecular markers (EGFR amplification, IDH1 mutation) to inform precision oncology strategies. Methods In a retrospective cohort of 1,016 adult patients with histologically confirmed gliomas (2015–2023) at the 10th Military Research Hospital, Bydgoszcz, Poland, we assessed T. gondii IgG seropositivity via ELISA and molecular markers (EGFR amplification, IDH1 mutation) using FISH, NGS, or qPCR, per WHO CNS5 classification. Chi-square tests, Fisher’s exact tests, and multivariate logistic regression (adjusted for age, sex, tumor grade, resection extent) evaluated associations. Primary outcomes were T. gondii seropositivity’s association with glioma grade and molecular profiles. Results Among 662 patients with serology data, T. gondii IgG seropositivity was significantly associated with high-grade gliomas (HGG; grades 3–4; 82.3% in seropositive vs. 66.0% in seronegative, χ²=25.612, p < 0.001; OR = 2.14, 95% CI: 1.48–3.09, p < 0.001). In 117 patients with EGFR data, seropositivity correlated with EGFR amplification (54.3% vs. 35.2%, p = 0.041; OR = 1.92, 95% CI: 1.02–3.61, p = 0.044). In 170 patients with IDH1 data, seropositivity was linked to IDH-wildtype status (90.4% vs. 69.1%, p = 0.001; OR = 0.29, 95% CI: 0.12–0.71, p = 0.007). No associations were found for T. gondii IgG titers (p = 0.079) or CRP (p = 0.201) with grade, but WBC counts correlated with progression (p < 0.001). Conclusion T. gondii IgG seropositivity is a potential prognostic biomarker for HGG and aggressive molecular profiles (EGFR amplification, IDH-wildtype), particularly in glioblastoma, supporting its integration into precision oncology diagnostics for prognostic stratification and targeted therapy development [12].