title: Gene expression mapping of histone deacetylases and co-factors, and correlation with survival time and 1H-HRMAS metabolomic profile in human gliomas.
abstract: Primary brain tumors are presently classified based on imaging and histopathological techniques, which remains unsatisfaying. We profiled here by quantitative real time PCR (qRT-PCR) the transcripts of eighteen histone deacetylases (HDACs) and a subset of transcriptional co-factors in non-tumoral brain samples from 15 patients operated for epilepsia and in brain tumor samples from 50 patients diagnosed with grade II oligodendrogliomas (ODII, n = 9), grade III oligodendrogliomas (ODIII, n = 22) and glioblastomas (GL, n = 19). Co-factor transcripts were significantly different in tumors as compared to non-tumoral samples and distinguished different molecular subgroups of brain tumors, regardless of tumor grade. Among all patients studied, the expression of HDAC1 and HDAC3 was inversely correlated with survival, whereas the expression of HDAC4, HDAC5, HDAC6, HDAC11 and SIRT1 was significantly and positively correlated with survival time of patients with gliomas. (1)H-HRMAS technology revealed metabolomically distinct groups according to the expression of HDAC1, HDAC4 and SIRT1, suggesting that these genes may play an important role in regulating brain tumorigenesis and cancer progression. Our study hence identified different molecular fingerprints for subgroups of histopathologically similar brain tumors that may enable the prediction of outcome based on the expression level of co-factor genes and could allow customization of treatment.
authors: 1] Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, 1 place de l'hôpital, 67091 Strasbourg Cedex, France [2] Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)/CNRS UMR 7104/INSERM U 964/Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France.
authors: Nassim
authors: N
authors: Dali-Youcef
authors: Department of Neurosurgery, Hôpitaux Universitaires de Strasbourg, avenue Molière, 67085 Strasbourg Cedex, France.
authors: Sébastien
authors: S
authors: Froelich
authors: Department of Biophysics and Nuclear Medicine, Hôpitaux Universitaires de Strasbourg, CHU de Hautepierre, avenue Molière, 67200 Strasbourg Cedex, France.
authors: François-Marie
authors: FM
authors: Moussallieh
authors: Department of Neurosurgery, Hôpitaux Universitaires de Strasbourg, avenue Molière, 67085 Strasbourg Cedex, France.
authors: Salvatore
authors: S
authors: Chibbaro
authors: Centre Paul Strauss, 3 rue de la porte de l'Hôpital 67065 Strasbourg, Cedex, France.
authors: Georges
authors: G
authors: Noël
authors: Department of Biophysics and Nuclear Medicine, Hôpitaux Universitaires de Strasbourg, CHU de Hautepierre, avenue Molière, 67200 Strasbourg Cedex, France.
authors: Izzie J
authors: IJ
authors: Namer
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)/CNRS UMR 7104/INSERM U 964/Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France.
authors: Sami
authors: S
authors: Heikkinen
authors: 1] Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)/CNRS UMR 7104/INSERM U 964/Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France [2] Institut Clinique de la Souris, 1 rue Laurent Fries, 67404 Illkirch, France.
authors: Johan
authors: J
authors: Auwerx
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics*; D020869:Gene Expression Profiling; D005910:Glioma / Q000201:enzymology / Q000235:genetics*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D055432:Metabolomics; D060888:Real-Time Polymerase Chain Reaction; D016019:Survival Analysis
chemical_list: D006655:Histone Deacetylases