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pmid:35202840
In-Depth Matrisome and Glycoproteomic Analysis of Human Brain Glioblastoma Versus Control Tissue.
Manveen K Sethi · Margaret Downs · Chun Shao · William E Hackett · Joanna J Phillips · Joseph Zaia
Molecular & cellular proteomics : MCP · 2022 doi:10.1016/j.mcpro.2022.100216
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Experiment
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Data
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Analysis
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Complete file
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Little attention, however, has been paid to glycosylation of the extracellular matrix components that constitute the majority of glycosylated protein mass and presumed biological properties. To acquire a comprehensive understanding of the biological functions of the matrisome and its components, including proteoglycans (PGs) and glycosaminoglycans (GAGs), in GBM tumorigenesis, and to identify potential biomarker candidates, we studied the alterations of GAGs, including heparan sulfate (HS) and chondroitin sulfate (CS), the core proteins of PGs, and other glycosylated matrisomal proteins in GBM subtypes versus control human brain tissue samples. We scrutinized the proteomics data to acquire in-depth site-specific glycoproteomic profiles of the GBM subtypes that will assist in identifying specific glycosylation changes in GBM. We observed an increase in CS 6-O sulfation and a decrease in HS 6-O sulfation, accompanied by an increase in unsulfated CS and HS disaccharides in GBM versus control samples. Several core matrisome proteins, including PGs (decorin, biglycan, agrin, prolargin, glypican-1, and chondroitin sulfate proteoglycan 4), tenascin, fibronectin, hyaluronan link protein 1 and 2, laminins, and collagens, were differentially regulated in GBM versus controls. Interestingly, a higher degree of collagen hydroxyprolination was also observed for GBM versus controls. Further, two PGs, chondroitin sulfate proteoglycan 4 and agrin, were significantly lower, about 6-fold for isocitrate dehydrogenase-mutant, compared to the WT GBM samples. Differential regulation of O-glycopeptides for PGs, including brevican, neurocan, and versican, was observed for GBM subtypes versus controls. Moreover, an increase in levels of glycosyltransferase and glycosidase enzymes was observed for GBM when compared to control samples. We also report distinct protein, peptide, and glycopeptide features for GBM subtypes comparisons. Taken together, our study informs understanding of the alterations to key matrisomal molecules that occur during GBM development. (Data are available via ProteomeXchange with identifier PXD028931, and the peaks project file is available at Zenodo with DOI 10.5281/zenodo.5911810).", "claims": [{"id": "claim-method", "statement": "For statistical analysis, the compare means function was used with a FDR to correct for multiple comparisons (35). 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We scrutinized the proteomics data to acquire in-depth site-specific glyco", "ed on the instrument (for both glycomics and proteomics) at the same time to avoid any sample handli", "d peptide retention time calibration mix for proteomic analysis and disaccharide standards for HS a", "e names and peak database search numbers for proteomics analysis. Detailed information on the cases,"], "order_basis": "paper_text_order:908", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["nd Statistical Rationale In total, 43 tissue microarray (TMA) cores were used; 39 consisted of GBM s"], "order_basis": "paper_text_order:2986", "id": "assay:2"}]}