Abstract 5368: The differences in molecular profiles and survival outcomes between early and late-onset glioblastoma

Abstract Background: Age influences glioblastoma's molecular characteristics, with the 2021 WHO classification distinguishing pediatric and adult gliomas due to differing molecular profiles and prognoses, as pediatric glioblastomas show unique genetic alterations compared to adults and have a lower rate of malignant transformation. Although the molecular differences and prognosis between pediatric-type and adult-type glioblastoma are well-studied, the impact of age on adult glioblastoma patients remains underexplored. Methods: Targeted DNA sequencing data from baseline tissue samples of 139 glioblastoma patients were analyzed. Additionally, clinical and sequencing data from 258 glioblastoma patients in the TCGA cohort were utilized for RNA expression and prognosis analyses. Kaplan-Meier survival curves were generated for the TCGA cohort, and the log-rank test was employed to compare survival times between subtypes. Results: Among all patients in the study cohort, 11 patients were classified as early-onset glioblastoma (age ≤ 40), and 128 patients were with late-onset glioblastoma (age > 40). The results show that TERT mutations (P = 0.006), MGMT methylation (P = 0.043), and chromosome 7 gain and 10 loss (P = 0.012) are significantly enriched in late-onset glioblastoma patients, whereas KIT amplifications (P = 0.043) are more prevalent in early-onset patients. Beyond these genetic distinctions, patients with late-onset glioblastoma (P = 0.030) and positive MGMT methylation status (P = 0.050) exhibit higher tumor mutation burdens. The expression levels of chemokine (P = 0.002), IL-17 (P = 0.002), JAK-STAT (P = 0.011), NF-kappa B (P = 0.002), PI3K-Akt (P = 0.027), and TNF signaling pathways (P = 0.002) are elevated in late-onset patients, whereas early-onset patients show higher CD4+ (P = 0.029) and CD8+ (P = 0.077) T cell infiltrations. Notably, both early- and late-onset glioblastoma patients exhibited comparable actionable mutation profiles, except for a higher incidence of BRAF mutations in the early-onset group (P = 0.031). Survival analysis further revealed that late-onset (mPFS: 13.0 months in late-onset vs. 30.0 months in early-onset; P < 0.001) and elevated TMB (mPFS: 13.6 months in TMB-high vs. 15.3 months in TMB-low, stratified by the median value; P = 0.043) were associated with a poorer prognosis in patients with glioblastoma. Conclusions: In summary, late-onset patients have a poorer prognosis, characterized by adverse biomarkers such as TERT promoter mutations and chromosome 7 gain and 10 loss, but are more likely to benefit from temozolomide chemotherapy, while early-onset patients, with a higher frequency of BRAF mutations, may have a higher chance respond to BRAF inhibitors. Citation Format: Hanlin Chen, Jiaohui Pang, Haimeng Tang, Xue Wu, Qiuxiang Ou. The differences in molecular profiles and survival outcomes between early and late-onset glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5368.