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Updated: Oct 9, 2025
A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas
Published on: May 9, 2025
Tissue metabolites in diffuse glioma and their modulations by IDH1 mutation, histology, and treatment
Christoph Trautwein1, Laimdota Zizmare1, Irina Mäurer2,3
1Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center.
Abstract:
The discovery of the oncometabolite 2-hydroxyglutarate in isocitrate dehydrogenase 1-mutated (IDH1-mutated) tumor entities affirmed the role of metabolism in cancer. However, large databases with tissue metabolites that are modulated by IDH1 mutation remain an area of development. Here, we present an unprecedented and valuable resource for tissue metabolites in diffuse glioma and their modulations by IDH1 mutation, histology, and tumor treatments in 101 tissue samples from 73 diffuse glioma patients (24 astrocytoma, 17 oligodendroglioma, 32 glioblastoma), investigated by NMR-based metabolomics and supported by RNA-Seq. We discovered comparison-specific metabolites and pathways modulated by IDH1 (IDH1 mutation status cohort) and tumor entity. The Longitudinal investigation cohort provides metabolic profiles of untreated and corresponding treated glioma samples at first progression. Most interestingly, univariate and multivariate cox regressions and Kaplan-Meier analyses revealed that tissue metabolites correlate with progression-free and overall survival. Thus, this study introduces potentially novel candidate prognostic and surrogate metabolite biomarkers for future prospective clinical studies, aiming at further refining patient stratification in diffuse glioma. Furthermore, our data will facilitate the generation of so-far-unanticipated hypotheses for experimental studies to advance our molecular understanding of glioma biology.
Insights
This study presents a valuable resource of tissue metabolites in diffuse glioma, revealing how IDH1 mutation, histology, and treatment impact them. These metabolites show potential as novel biomarkers for predicting patient survival and refining glioma classification.
Area of Science:
- Oncometabolomics
- Cancer Metabolism
- Neuro-oncology
Background:
- The role of metabolism in cancer is highlighted by oncometabolites like 2-hydroxyglutarate in IDH1-mutated tumors.
- A need exists for comprehensive databases detailing tissue metabolites affected by IDH1 mutations in diffuse gliomas.
Purpose of the Study:
- To create a resource of tissue metabolites in diffuse glioma.
- To investigate the modulation of these metabolites by IDH1 mutation status, histology, and treatment.
- To identify metabolite biomarkers correlating with patient survival.
Main Methods:
- NMR-based metabolomics and RNA-Seq on 101 diffuse glioma tissue samples from 73 patients.
- Analysis of metabolic profiles based on IDH1 mutation status, tumor entity, and longitudinal treatment data.
- Statistical analyses including Cox regressions and Kaplan-Meier survival analyses.
Main Results:
- Identification of specific metabolites and pathways modulated by IDH1 mutation and glioma histology.
- Metabolic profiles of untreated and treated glioma samples at progression were characterized.
- Tissue metabolites were found to correlate significantly with progression-free and overall survival.
Conclusions:
- The study provides a novel resource for diffuse glioma metabolomics, offering insights into IDH1 mutation and treatment effects.
- Identified tissue metabolites represent potential prognostic and surrogate biomarkers for patient stratification.
- The findings pave the way for future clinical studies and advance the molecular understanding of glioma biology.
