title: Quantitative proteomic Isotope-Coded Protein Label (ICPL) analysis reveals alteration of several functional processes in the glioblastoma.
abstract: Glioblastoma (GB), the most frequent primary tumor of the central nervous system, remains one of the most lethal human cancers despite intensive researches. Current paradigm in the study of GB has been focused on inter-patient variability and on trying to isolate new classification elements or prognostic factors. Here, using ICPL, a technique for protein relative quantification by mass spectrometry, we investigated protein expression between the four regions of GB on clinically relevant biopsies from 5 patients. We identified 584 non-redundant proteins and 31 proteins were found to be up-regulated in the tumor region compared to the peri-tumoral brain tissue, among which, 24 proteins belong to an interaction network linked to 4 biological processes. The core of this network is mainly constituted of interactions between beta-actin (ACTB) with heat shock proteins (HSP90AA1, HSPA8) and 14-3-3 proteins (YWHAZ, YWHAG, YWHAB). A cluster of three isoforms of the sodium pump α-subunit (ATP1A1, ATP1A2, ATP1A3) was also identified outside this network. The differential expression observed for ACTB and 14-3-3γ was further validated by western blot and/or immunohistochemistry. Our study confirms the identity of previously proposed molecular targets, highlights several functional processes altered in GB such as energy metabolism and synaptic transmission and could thus provide added value to new therapeutic trails.
authors.affiliation: Proteomics Core Facility Biogenouest, IRSET, Inserm U1085, Campus de Beaulieu, F-35042 Rennes, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Com
authors.forename: Anne
authors.initials: A
authors.lastname: Clavreul
authors.forename: Mélanie
authors.initials: M
authors.lastname: Lagarrigue
authors.forename: Sophie
authors.initials: S
authors.lastname: Michalak
authors.forename: Philippe
authors.initials: P
authors.lastname: Menei
authors.forename: Charles
authors.initials: C
authors.lastname: Pineau
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D002247:Carbon Isotopes; D003903:Deuterium; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D009363:Neoplasm Proteins / Q000032:analysis*; D009419:Nerve Tissue Proteins / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D048948:14-3-3 Proteins; D000199:Actins; D002247:Carbon Isotopes; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D003903:Deuterium