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Updated: Feb 28, 2026
A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas
Published on: May 9, 2025
Proteomics in IDH-mutated diffuse lower-grade glioma: a scoping review
Carl-Johan Kihlstedt1, Anna Dénes1, Alireza Mansouri2
1Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Background:
Therapeutic options and biomarkers for isocitrate dehydrogenase-mutated (IDHmut) diffuse lower-grade glioma (dLGG), WHO grade 2-3, are limited. Global quantitative proteomics has aided the discovery of novel markers and drug targets across various pathologies. This review aimed to summarize current proteomic findings in IDHmut dLGG.
Methods:
PubMed, Embase, and Scopus were searched following PRISMA-ScR guidelines. Studies examining quantitative proteomics in IDHmut dLGG with liquid chromatography-mass spectrometry in adult human samples were included. Studies with only high-grade gliomas, without IDHmut, using xenografts, or cell line samples, and reviews were excluded.
Results:
In total, 1,902 records were identified; 85 full-texts were retrieved, and 13 met the inclusion criteria. Twelve studies were cross-sectional and one longitudinal. Two studies used cerebrospinal fluid samples, while seven used fresh frozen and five formalin-fixed paraffin-embedded (FFPE) tissue samples. There was a large heterogeneity in aims, sample types, and analytical techniques. The most recurrent finding was altered energy metabolism, mostly related to the tricarboxylic acid cycle, compared to IDH-wildtype gliomas. IDHmut dLGG proteomic profile was distinct from other brain tumors, including IDH-wildtype glioblastoma, IDHmut grade 4 astrocytomas, and grade 1 gliomas or normal brain.
Conclusions:
IDHmut dLGG has a unique proteome that may be leveraged for biomarkers and therapeutic discovery. Proteomic findings indicate a particular dependency on glutamate metabolism to sustain the citric acid cycle and energy production. Although current proteomic knowledge is limited and fragmented, technological advancements present an opportunity for large-scale studies using FFPE samples, advancing proteomic knowledge and precision medicine in IDHmut dLGG.
