PT  - JOURNAL ARTICLE
AU  - Djuric, Ugljesa
AU  - Lam, K. H. Brian
AU  - Kao, Jennifer
AU  - Batruch, Ihor
AU  - Jevtic, Stefan
AU  - Papaioannou, Michail-Dimitrios
AU  - Diamandis, Phedias E
TI  - Defining protein pattern differences among molecular subtypes of diffuse gliomas using mass spectrometry
AID  - 10.1074/mcp.RA119.001521
DP  - 2019 Jan 01
TA  - Molecular & Cellular Proteomics
PG  - mcp.RA119.001521
4099  - http://www.mcponline.org/content/early/2019/07/28/mcp.RA119.001521.short
4100  - http://www.mcponline.org/content/early/2019/07/28/mcp.RA119.001521.full
AB  - 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 3 glioma cohorts subclassified largely based on their IDH and 1p19q co-deletion status (IDH wildtype (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 tumour 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 to IDH-matched glioblastoma 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 dependant 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.