title: Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme.
abstract: The goal of this study was to identify correlations between metabolites from proton MR spectroscopy and genetic pathway activity in glioblastoma multiforme (GBM). Twenty patients with primary GBM were analysed by short echo-time chemical shift imaging and genome-wide expression analyses. Weighed Gene Co-Expression Analysis was used for an integrative analysis of imaging and genetic data. N-acetylaspartate, normalised to the contralateral healthy side (nNAA), was significantly correlated to oligodendrocytic and neural development. For normalised creatine (nCr), a group with low nCr was linked to the mesenchymal subtype, while high nCr could be assigned to the proneural subtype. Moreover, clustering of normalised glutamine and glutamate (nGlx) revealed two groups, one with high nGlx being attributed to the neural subtype, and one with low nGlx associated with the classical subtype. Hence, the metabolites nNAA, nCr, and nGlx correlate with a specific gene expression pattern reflecting the previously described subtypes of GBM. Moreover high nNAA was associated with better clinical prognosis, whereas patients with lower nNAA revealed a shorter progression-free survival (PFS).
authors.affiliation: Department of Neurosurgery, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Dieter Henrik
authors.initials: DH
authors.lastname: Heiland
authors.affiliation: Department of Neuroradiology, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Mader
authors.affiliation: Institute for Medical Biometry and Statistics, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Schlosser
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pfeifer
authors.affiliation: Department of Neurosurgery, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Maria Stella
authors.initials: MS
authors.lastname: Carro
authors.affiliation: Department of Medical Physics, Diagnostic Radiology, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lange
authors.affiliation: Department of Neuroradiology, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schwarzwald
authors.affiliation: Department of Neurosurgery, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vasilikos
authors.affiliation: Department of Neuroradiology, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Urbach
authors.affiliation: Department of Neurosurgery, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Weyerbrock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D019295:Computational Biology / Q000379:methods*; D003401:Creatine / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D009363:Neoplasm Proteins; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D003401:Creatine