Grade-Specific Influences of MGMT and TERT Genes on the Prognosis of Glioma

Objective: To investigate the combined prognostic effects of MGMT expression/promoter methylation and TERT expression in gliomas across different grades (II, III, and IV) and evaluate their clinical implications. Methods: This study analyzed 454 low-grade glioma (LGG; grades II/III) and 162 glioblastoma (GBM; grade IV) samples from The Cancer Genome Atlas (TCGA) to evaluate the prognostic roles of MGMT (expression and promoter methylation) and TERT (expression) across glioma grades. Survival analyses were performed using R packages survivalROC and survminer, with Kaplan-Meier curves generated to visualize survival differences between risk groups stratified by MGMT and TERT status. Log-rank tests were applied to statistically compare survival outcomes. A combined risk score integrating MGMT methylation/expression and TERT expression was developed to assess their synergistic prognostic effects. Statistical significance was defined as p < 0.05. Result: Analysis revealed grade-specific prognostic associations for MGMT and TERT: in grade II gliomas, neither MGMT (expression/methylation) nor TERT expression, nor their combined score, showed significant survival correlations. In grade III tumors, lower TERT expression was associated with prolonged survival (p < 0.05), while MGMT and the combined score remained non-prognostic. Notably, in grade IV glioblastomas (GBM), both MGMT methylation/expression and the combined MGMT-TERT score significantly predicted survival outcomes (p < 0.01), with higher combined scores indicating poorer prognosis. These findings highlight divergent roles of MGMT and TERT across glioma grades, emphasizing their synergistic prognostic relevance in high-grade disease. Conclusion: MGMT and TERT exert distinct prognostic impacts across glioma grades: Grade II gliomas showed no survival association with MGMT (expression/methylation), TERT expression, or their combined score, while Grade III tumors revealed prolonged survival linked to lower TERT expression (p < 0.05), with MGMT and the combined score remaining non-prognostic. In contrast, Grade IV glioblastomas (GBM) demonstrated significant survival correlations for both MGMT (methylation/expression) and the MGMT-TERT combined score (p < 0.01), where higher combined scores predicted poorer outcomes. These findings highlight the grade-specific roles of MGMT and TERT in glioma progression, underscoring their potential utility in personalized clinical decision-making for high-grade gliomas.