Defining Protein Pattern Differences Among Molecular Subtypes of Diffuse Gliomas Using Mass Spectrometry*[S]
| Autor: | Jennifer Kao, K. H. Brian Lam, Ugljesa Djuric, Phedias Diamandis, Michail-Dimitrios Papaioannou, Ihor Batruch, Stefan D Jevtic |
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| Rok vydání: | 2019 |
| Předmět: |
Proteomics
Biology Serpin Biochemistry Analytical Chemistry Transcriptome 03 medical and health sciences Tandem Mass Spectrometry Glioma Tumor Cells Cultured medicine Cluster Analysis Humans Protein Interaction Maps Epithelial–mesenchymal transition Molecular Biology 030304 developmental biology 0303 health sciences Brain Neoplasms Sequence Analysis RNA Research 030302 biochemistry & molecular biology Wild type medicine.disease Phenotype Isocitrate Dehydrogenase Chromosomes Human Pair 1 Tissue Array Analysis Mutation RNA splicing Proteome Neoplastic Stem Cells Cancer research Chromosome Deletion Chromosomes Human Pair 19 Chromatography Liquid |
| Zdroj: | Mol Cell Proteomics |
| ISSN: | 1535-9476 |
| Popis: | Molecular characterization of diffuse gliomas has thus far largely focused on genomic and transcriptomic interrogations. Here, we utilized mass spectrometry and overlay protein-level information onto genomically defined cohorts of diffuse gliomas to improve our downstream molecular understanding of these lethal malignancies. Bulk and macrodissected tissues were utilized to quantitate 5,496 unique proteins over three glioma cohorts subclassified largely based on their IDH and 1p19q codeletion status (IDH wild type (IDHwt), n = 7; IDH mutated (IDHmt), 1p19q non-codeleted, n = 7; IDH mutated, 1p19q-codeleted, n = 10). Clustering analysis highlighted proteome and systems-level pathway differences in gliomas according to IDH and 1p19q-codeletion status, including 287 differentially abundant proteins in macrodissection-enriched tumor specimens. IDHwt tumors were enriched for proteins involved in invasiveness and epithelial to mesenchymal transition (EMT), while IDHmt gliomas had increased abundances of proteins involved in mRNA splicing. Finally, these abundance changes were compared with IDH-matched GBM stem-like cells (GSCs) to better pinpoint protein patterns enriched in putative cellular drivers of gliomas. Using this integrative approach, we outline specific proteins involved in chloride transport (e.g. chloride intracellular channel 1, CLIC1) and EMT (e.g. procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3, PLOD3, and serpin peptidase inhibitor clade H member 1, SERPINH1) that showed concordant IDH-status-dependent abundance differences in both primary tissue and purified GSC cultures. Given the downstream position proteins occupy in driving biology and phenotype, understanding the proteomic patterns operational in distinct glioma subtypes could help propose more specific, personalized, and effective targets for the management of patients with these aggressive malignancies. |
| Databáze: | OpenAIRE |
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