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    A Robust and Versatile Automated Glycoanalytical Technology for Serum Antibodies and Acute Phase Proteins: Ovarian Cancer Case Study


    O'Flaherty, Roisin and Muniyappa, Mohankumar and Walsh, Ian and Stockmann, Henning and Hilliard, Mark and Hutson, Richard and Saldova, Radka and Rudd, Pauline M. (2019) A Robust and Versatile Automated Glycoanalytical Technology for Serum Antibodies and Acute Phase Proteins: Ovarian Cancer Case Study. Molecular and Cellular Proteomics (MCP), 18 (11). pp. 1-31. ISSN 1535-9476

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    Abstract

    The direct association of the genome, transcriptome, metabolome, lipidome and proteome with the serum glycome has revealed systems of interconnected cellular pathways. The exact roles of individual glycoproteomes in the context of disease have yet to be elucidated. In a move towards personalized medicine, it is now becoming critical to understand disease pathogenesis, and the traits, stages, phenotypes and molecular features that accompany it, as the disruption of a whole system. To this end, we have developed an innovative technology on an automated platform, "GlycoSeqCap", which combines N-glycosylation data from six glycoproteins using a single source of human serum. Specifically, we multiplexed and optimised a successive serial capture and glycoanalysis of six purified glycoproteins, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), transferrin (Trf), haptoglobin (Hpt) and alpha-1-antitrypsin (A1AT), from 50µl of human serum. We provide the most comprehensive and in-depth glycan analysis of individual glycoproteins in a single source of human serum to date. To demonstrate the technological application in the context of a disease model, we performed a pilot study in an ovarian cancer cohort (n=34) using discrimination and classification analyses to identify aberrant glycosylation. In our sample cohort, we exhibit improved selectivity and specificity over the currently used biomarker for ovarian cancer, CA-125, for early stage ovarian cancer. This technology will establish a new state-of-the-art strategy for the characterization of individual serum glycoproteomes as a diagnostic and monitoring tool which represents a major step towards understanding the changes that take place during disease.

    Item Type: Article
    Keywords: robust; versatile; automated; glycoanalytical; technology; serum; antibodies; acute phase proteins; ovarian cancer;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 15018
    Identification Number: https://doi.org/10.1074/mcp.RA119.001531
    Depositing User: Roisin O'Flaherty
    Date Deposited: 15 Nov 2021 17:08
    Journal or Publication Title: Molecular and Cellular Proteomics (MCP)
    Publisher: Elsevier
    Refereed: Yes
    URI:

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