The integrative metabolomic-transcriptomic landscape of glioblastome multiforme

// Dieter Henrik Heiland 1, 5 , Jakob Worner 2 , Jan Gerrit Haaker 1, 5 , Daniel Delev 1, 5 , Nils Pompe 2 , Bianca Mercas 1, 5 , Pamela Franco 1, 5 , Annette Gabelein 1, 5 , Sabrina Heynckes 1, 5 , Dietmar Pfeifer 3, 5 , Stefan Weber 2 , Irina Mader 4, 5 and Oliver Schnell 1, 5 1 Department of Neurosurgery, Medical Center, University of Freiburg, Freiburg, Germany 2 Institute of Physical Chemistry, Faculty of Chemistry and Pharmacy, University of Freiburg, Freiburg, Germany 3 Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, University of Freiburg, Freiburg, Germany 4 Department of Neuroradiology, Medical Center, University of Freiburg, Freiburg, Germany 5 Faculty of Medicine, University of Freiburg, Freiburg, Germany Correspondence to: Dieter Henrik Heiland, email: dieter.henrik.heiland@uniklinik-freiburg.de Keywords: metabolomics, transcriptomics, network analysis, glioblastoma multiforme, WGCNA Received: January 02, 2017     Accepted: February 23, 2017     Published: March 24, 2017 ABSTRACT The purpose of this study was to map the landscape of metabolic-transcriptional alterations in glioblastoma multiforme. Omic-datasets were acquired by metabolic profiling (1D-NMR spectroscopy n=33 Patient) and transcriptomic profiling (n=48 Patients). Both datasets were analyzed by integrative network modeling. The computed model concluded in four different metabolic-transcriptomic signatures containing: oligodendrocytic differentiation, cell-cycle functions, immune response and hypoxia. These clusters were found being distinguished by individual metabolism and distinct transcriptional programs. The study highlighted the association between metabolism and hallmarks of oncogenic signaling such as cell-cycle alterations, immune escape mechanism and other cancer pathway alterations. In conclusion, this study showed the strong influence of metabolic alterations in the wide scope of oncogenic transcriptional alterations.