Gene Expression Profiling Stratifies IDH1-Mutant Glioma with Distinct Prognoses

Area of Science:

• Neuro-oncology
• Cancer Genomics
• Molecular Pathology

Background:

• Isocitrate dehydrogenase (IDH)1 mutations are key genetic events in glioma.
• Genome-wide expression alterations linked to IDH1 status require systematic profiling.

Purpose of the Study:

• To profile genome-wide gene expression alterations associated with IDH1 mutation in glioma.
• To develop a robust gene signature for prognostic stratification of IDH1-mutant glioma patients.

Main Methods:

• RNA-sequencing data from Chinese Glioma Genome Atlas (310 patients) and validation cohorts (297 internal, 205 external).
• Differential gene expression analysis based on IDH1 mutation status.
• Development and validation of a six-gene risk signature.

Main Results:

• Distinct gene expression profiles identified between IDH1-mutant and wild-type gliomas.
• A six-gene signature accurately distinguished low- from high-risk IDH1-mutant low-grade gliomas (LGG) and glioblastomas (GBM).
• The signature demonstrated independent prognostic value and superior predictive accuracy over traditional factors.

Conclusions:

• IDH1 mutation induces conserved gene expression patterns across glioma grades.
• The six-gene signature provides precise risk stratification for IDH1-mutant glioma.
• Integration of the signature with clinical factors enhances glioma patient management.