| Autor: |
Andrew J. Scott, Luis O. Correa, Yilun Sun, Visweswaran Ravikumar, Anthony C. Andren, Li Zhang, Sudharsan Srinivasan, Neil Jairath, Kait Verbal, Karin Muraszko, Oren Sagher, Shannon A. Carty, Shawn Hervey-Jumper, Daniel Orringer, Michelle M. Kim, Larry Junck, Yoshie Umemura, Denise Leung, Sriram Venneti, Sandra Camelo-Piragua, Theodore S. Lawrence, Joseph E. Ippolito, Wajd N. Al-Holou, Prakash Chinnaiyan, Jason Heth, Arvind Rao, Costas A. Lyssiotis, Daniel R. Wahl |
| Rok vydání: |
2022 |
| Popis: |
AimsTargeting tumor metabolism may improve the outcomes for patients with glioblastoma (GBM). To further preclinical efforts targeting metabolism in GBM, we tested the hypothesis that brain tumors can be stratified into distinct metabolic groups with different patient outcomes. Therefore, to determine if tumor metabolites relate to patient survival, we profiled the metabolomes of human gliomas and correlated metabolic information with clinical data.ResultsWe found that isocitrate dehydrogenase-wildtype (IDHwt) GBMs are metabolically distinguishable from IDH mutated (IDHmut) astrocytomas and oligodendrogliomas. Survival of patients with IDHmut gliomas was expectedly more favorable than those with IDHwt GBM, and metabolic signatures can stratify IDHwt GBMs subtypes with varying prognoses. Patients whose GBMs were enriched in amino acids had improved survival while those whose tumors were enriched for nucleobases and carbohydrates fared more poorly. These findings were recapitulated in validation cohorts using both metabolomic and transcriptomic data.InnovationOur results suggest the existence of metabolic subtypes of GBM with differing prognoses and further support the concept that metabolism may drive the aggressiveness of human gliomas.ConclusionsOur data show that metabolic signatures of human gliomas can inform patient survival. These findings may be used clinically to tailor novel metabolically targeted agents for GBM patients with different metabolic phenotypes. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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