Research Background
Glioma, as the most common primary intracranial malignant tumor, is characterized by high recurrence and disability rates, posing a serious threat to patients’ quality of life. Among them, glioblastoma (GBM) is the most aggressive subtype; even with standard treatment involving surgery combined with radiotherapy and chemotherapy, the median survival time remains less than 15 months. Traditional histopathological classification can no longer meet the demands for personalized diagnosis and treatment in the era of precision medicine. The 2021 WHO Classification of Tumors of the Central Nervous System incorporates molecular markers such as IDH1/2 mutations and 1p/19q co-deletion into diagnostic criteria, marking the entry of glioma management into the era of molecular subtyping. Furthermore, significant differences exist between Chinese and Western glioma patients in terms of age of onset, molecular profiles, clinical management, and survival outcomes, highlighting the urgent need to establish a large-scale clinical and molecular characteristic database based on the Chinese population.
Research Progress
This study reclassified patients according to modern WHO Classification criteria by integrating multi-dimensional molecular markers. It thoroughly investigated the clinical and molecular disparities between contemporary and historical cohorts, the distinct mutational signatures across different glioma subtypes and magnetic resonance imaging (MRI) features, and the subtype-dependent determinants affecting overall survival (OS). This provides valuable evidence-based medical guidance for the diagnosis and treatment of regional gliomas.
Key findings include:
1. Molecular subtyping reshapes diagnosis: Based on the WHO 2021 criteria, molecular testing led to altered diagnoses in 23.7% of cases, highlighting the limitations of traditional pathology.
2. Pathway co-activation patterns: Glioblastoma exhibited features of multi-pathway collaborative activation, particularly co-activation of the p53 and cell cycle pathways, with the highest average number of activated pathways (mean: 2.17). In contrast, oligodendrogliomas showed the lowest pathway activation (mean: 0.42). Moreover, activations of upstream and downstream genes within the same pathway displayed mutually exclusive patterns.
3. Strong anatomical-molecular correlations: IDH1/2 mutations were present in 63.5% of frontal lobe gliomas, while temporal lobe gliomas (80.3%) and thalamic/basal ganglia gliomas (90.4%) were predominantly IDH1/2 wild-type. Among younger patients (<46 years), 63.5% of frontal lobe gliomas harbored IDH1/2 mutations, whereas among older patients (≥46 years), temporal lobe (91.4%) and thalamic/basal ganglia (100%) gliomas were primarily IDH1/2 wild-type.
4. Validation of prognostic markers: TERT promoter mutations acted as a protective factor in IDH-mutant gliomas but indicated poor prognosis in IDH wild-type gliomas.
5. Chinese population-specific data: The median survival time in this study cohort was longer than that in historical cohorts from the TCGA database, suggesting advancements in treatment and potential population differences.
Future Perspectives
This study not only validates the necessity of molecular subtyping in the precise diagnosis and treatment of gliomas but also provides high-quality real-world data support for clinical research and individualized therapy of gliomas in the Chinese population. Several directions warrant further in-depth exploration in the future: (1) Multi-center prospective validation: As the current study is a single-center retrospective analysis, future efforts should involve collaboration across multiple hospitals, incorporating samples from broader geographical regions and ethnic groups to promote an integrated molecular-anatomical-clinical diagnostic and therapeutic model. (2) Longitudinal dynamic monitoring: The study did not cover treatment response and recurrence evolution. Future research should implement time-series sampling, combining ctDNA or radiomics to track clonal evolution and drug resistance mechanisms in real time. (3) Mechanisms of the anatomical microenvironment: Why do IDH-mutant gliomas "prefer" the frontal lobe? Further investigation is needed into how the epigenetic characteristics and metabolic microenvironment of neural precursor cells in this region drive the selection of mutant clones. (4) Optimization of treatment strategies: Based on pathway co-activation and mutual exclusivity patterns, exploration of combination drug strategies (e.g., PI3K/MET inhibitors) and conducting clinical trials for validation are essential.
Sources: https://spj.science.org/doi/10.34133/research.1014
Research
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Contemporary Precision Stratification and Prognostic Features of Primary Gliomas in a Southern Chinese Population
9-Dec-2025