title: The metabolomic signature of malignant glioma reflects accelerated anabolic metabolism.
abstract: Although considerable progress has been made toward understanding glioblastoma biology through large-scale genetic and protein expression analyses, little is known about the underlying metabolic alterations promoting their aggressive phenotype. We conducted global metabolomic profiling on patient-derived glioma specimens and identified specific metabolic programs differentiating low- and high-grade tumors, with the metabolic signature of glioblastoma reflecting accelerated anabolic metabolism. When coupled with transcriptional profiles, we identified the metabolic phenotype of the mesenchymal subtype to consist of accumulation of the glycolytic intermediate phosphoenolpyruvate and decreased pyruvate kinase activity. Unbiased hierarchical clustering of metabolomic profiles identified three subclasses, which we term energetic, anabolic, and phospholipid catabolism with prognostic relevance. These studies represent the first global metabolomic profiling of glioma, offering a previously undescribed window into their metabolic heterogeneity, and provide the requisite framework for strategies designed to target metabolism in this rapidly fatal malignancy.
authors.affiliation: Department of Radiation Oncology, Experimental Therapeutics, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA. prakash.chinnaiyan@moffitt.org
authors.forename: Prakash
authors.initials: P
authors.lastname: Chinnaiyan
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kensicki
authors.forename: Gregory
authors.initials: G
authors.lastname: Bloom
authors.forename: Antony
authors.initials: A
authors.lastname: Prabhu
authors.forename: Bhaswati
authors.initials: B
authors.lastname: Sarcar
authors.forename: Soumen
authors.initials: S
authors.lastname: Kahali
authors.forename: Steven
authors.initials: S
authors.lastname: Eschrich
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Qu
authors.forename: Peter
authors.initials: P
authors.lastname: Forsyth
authors.forename: Robert
authors.initials: R
authors.lastname: Gillies
mesh_terms: D008401:Gas Chromatography-Mass Spectrometry; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D055432:Metabolomics; D060787:Neoplasm Grading; D010641:Phenotype; D010728:Phosphoenolpyruvate / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D010728:Phosphoenolpyruvate; D011770:Pyruvate Kinase