METB-05. A metabolism-associated prognostic signature defines subtypes of glioma with IDH-mutation

Abstract Background We have acknowledged that glioma has molecular heterogeneity and metabolic reprogramming. So far, most studies are focused on the metabolic subtyping of different-grade or pathology gliomas. However, this study aims to find a novel classification based on metabolic gene expression profiles in IDH-mutant gliomas. Methods 973 patients with IDH-mutant diffuse gliomas were recruited from three databases. 373 patients in TCGA were selected to get novel metabolic subtypes using consensus cluster analysis, and 600 patients from the CGGA and GLASS were used for validation. The clinical features, immune infiltration, and metabolic features of each subtype were revealed by different analyses. Then we found a metabolic-related signature that could predict prognostic risk. Further, we analyzed this signature’s drug sensitivity using the CGP2014 drug library to explore the potentially sensitive drugs. Results We identified three highly distinct metabolic subtypes in IDH-mutant gliomas. The novel subtype shows different prognostic(p 0.05). In the cluster 1 subtype, carbohydrate metabolism and nucleotide metabolism were upregulated. In the cluster 2 subtype, amino acid and lipid metabolism were upregulated; in the cluster 3 subtype, lipid metabolism, nucleotide metabolism, and vitamin metabolism were upregulated. Besides, we found three metabolic subtypes correlated with diverse immune infiltration. We composed a metabolism-related signature with 13 genes and screened sensitive drugs for the different patients based on their risk score. Conclusions Our study provided a novel metabolic subtype for IDH-mutant glioma and highlighted the metabolic heterogeneity and potential therapeutic strategies for these patients.