# Proteomics in IDH-mutated diffuse lower-grade glioma: a scoping review

## TL;DR

This review summarizes proteomic findings in IDH-mutated lower-grade gliomas, highlighting unique metabolic patterns and potential for new biomarkers and therapies.

## Contribution

The study provides a comprehensive scoping review of proteomic research in IDH-mutated diffuse lower-grade gliomas, identifying key metabolic differences and research gaps.

## Key findings

- IDH-mutated dLGG has a distinct proteome compared to other brain tumors.
- Altered energy metabolism, particularly in the tricarboxylic acid cycle, is a common finding.
- Proteomic profiles suggest a dependency on glutamate metabolism in IDH-mutated dLGG.

## Abstract

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.

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.

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.

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.