Metabolomic profiles of human glioma inform patient survival
Authors
Andrew J. Scott, University of Michigan, 1259, Ann Arbor, Michigan, United States; andsco@med.umich.edu.
Luis O. Correa, University of Michigan, 1259, Ann Arbor, Michigan, United States; lcorrea@umich.edu.
Donna Edwards, University of Michigan, 1259, Ann Arbor, Michigan, United States; dmed@med.umich.edu.
Yilun Sun, Case Western Reserve University, 2546, Cleveland, Ohio, United States; yxs1212@case.edu.
Visweswaran Ravikumar, University of Michigan, 1259, Ann Arbor, Michigan, United States; vravik@umich.edu.
Anthony C. Andren, University of Michigan, 1259, Ann Arbor, Michigan, United States; acandren@umich.edu.
Li Zhang, University of Michigan, 1259, Ann Arbor, Michigan, United States; lzhangok@med.umich.edu.
Sudharsan Srinivasan, University of Michigan, 1259, Ann Arbor, Michigan, United States; sudhu@med.umich.edu.
Neil Jairath, University of Michigan, 1259, Ann Arbor, Michigan, United States; jairathn@umich.edu.
Kait Verbal, University of Michigan, 1259, Ann Arbor, Michigan, United States; kaitmcm@med.umich.edu.
Karin Muraszko, University of Michigan, 1259, Ann Arbor, Michigan, United States; karinm@med.umich.edu.
Oren Sagher, University of Michigan, 1259, Ann Arbor, Michigan, United States; osagher@med.umich.edu.
Shannon A. Carty, University of Michigan, 1259, Ann Arbor, Michigan, United States; scarty@med.umich.edu.
Shawn Hervey-Jumper, University of California San Francisco, 8785, San Francisco, California, United States; shawn.hervey-jumper@ucsf.edu.
Daniel Orringer, NYU Langone Health, 12297, New York, New York, United States; Daniel.Orringer@nyulangone.org.
Michelle M. Kim, University of Michigan, 1259, Ann Arbor, Michigan, United States; michekim@med.umich.edu.
Larry Junck, University of Michigan, 1259, Ann Arbor, Michigan, United States; ljunck@med.umich.edu.
Yoshie Umemura, University of Michigan, 1259, Ann Arbor, Michigan, United States; yoshie@med.umich.edu.
Denise Leung, University of Michigan, 1259, Ann Arbor, Michigan, United States; ledenise@med.umich.edu.
Sriram Venneti, University of Michigan, 1259, Ann Arbor, Michigan, United States; svenneti@med.umich.edu.
Sandra Camelo-Piragua, University of Michigan, 1259, Ann Arbor, Michigan, United States; sandraca@med.umich.edu.
Theodore S. Lawrence, University of Michigan, 1259, Ann Arbor, Michigan, United States; tsl@med.umich.edu.
Joseph E. Ippolito, Washington University in St Louis, 7548, St Louis, Missouri, United States; ippolitoj@wustl.edu.
Wajd N. Al-Holou, University of Michigan, 1259, Ann Arbor, Michigan, United States; wna@med.umich.edu.
Prakash Chinnaiyan, Beaumont Health System, 7005, Royal Oak, Michigan, United States; Prakash.Chinnaiyan2@beaumont.org.
Jason Heth, University of Michigan, 1259, Ann Arbor, Michigan, United States; jheth@med.umich.edu.
Arvind Rao, University of Michigan, 1259, Ann Arbor, Michigan, United States; ukarvind@med.umich.edu.
Costas A. Lyssiotis, University of Michigan, 1259, Ann Arbor, Michigan, United States; clyssiot@med.umich.edu.
Daniel R. Wahl, University of Michigan, 1259, Ann Arbor, Michigan, United States; dwahl@med.umich.edu.
Abstract
AIMS: Targeting 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. RESULTS: We 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 nucleotides, redox molecules and lipid metabolites fared more poorly. These findings were recapitulated in validation cohorts using both metabolomic and transcriptomic data. INNOVATION: Our 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. CONCLUSIONS: Our 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.
Publication Date
2-27-2023
Publication Title
Antioxidants & redox signaling
Digital Object Identifier (DOI)
10.1089/ars.2022.0085
Recommended Citation
Scott, Andrew J.; Correa, Luis O.; Edwards, Donna; Sun, Yilun; Ravikumar, Visweswaran; Andren, Anthony C.; Zhang, Li; Srinivasan, Sudharsan; Jairath, Neil; Verbal, Kait; Muraszko, Karin; Sagher, Oren; Carty, Shannon A.; Hervey-Jumper, Shawn; Orringer, Daniel; Kim, Michelle M.; Junck, Larry; Umemura, Yoshie; Leung, Denise; Venneti, Sriram; Camelo-Piragua, Sandra; Lawrence, Theodore S.; Ippolito, Joseph E.; Al-Holou, Wajd N.; Chinnaiyan, Prakash; Heth, Jason; Rao, Arvind; Lyssiotis, Costas A.; and Wahl, Daniel R., "Metabolomic profiles of human glioma inform patient survival" (2023). Neurology. 1452.
https://scholar.barrowneuro.org/neurology/1452
