Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme

Sci Rep. 2016 Jun 28:6:29052. doi: 10.1038/srep29052.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Computational Biology / methods*
  • Creatine / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genome-Wide Association Study
  • Glioblastoma / diagnostic imaging*
  • Glioblastoma / genetics
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neurons / metabolism
  • Neurons / pathology
  • Oligodendroglia / metabolism
  • Oligodendroglia / pathology
  • Prognosis
  • Prospective Studies
  • Survival Analysis

Substances

  • Neoplasm Proteins
  • Glutamine
  • Aspartic Acid
  • Glutamic Acid
  • N-acetylaspartate
  • Creatine