4.5 Article

Identification of blood-protein carriers of the CA 19-9 antigen and characterization of prevalence in pancreatic diseases

Journal

PROTEOMICS
Volume 11, Issue 18, Pages 3665-3674

Publisher

WILEY-BLACKWELL
DOI: 10.1002/pmic.201000827

Keywords

Antibody arrays; CA 19-9; Glycoproteomics; Glycosylation; Pancreatic cancer

Funding

  1. National Cancer Institute [R33 CA122890]
  2. Van Andel Research Institute

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The current best serum marker for pancreatic cancer, CA 19-9, detects a carbohydrate antigen on multiple protein carriers. Better knowledge of the protein carriers of the CA 19-9 antigen in various disease states may lead to improved diagnostic tests. To identify proteins that carry the CA 19-9 antigen, we immunoprecipitated the CA 19-9 antigen from pooled sera and identified the associated proteins using MS. Among the high-confidence identifications, we confirmed the presence of the CA 19-9 antigen on Apolipoprotein B-100 by antibody arrays and Western blot and on kininogen, ARVCF, and Apolipoprotein E by antibody arrays. We characterized the frequency and levels of the CA 19-9 antigen on the four proteins across various patient groups (pancreatic cancer, pancreatitis, and healthy controls) using antibody arrays. Nearly, 10-25% of the subjects showed elevations of the antigen on each protein, but the elevations were not associated with disease state or total CA 19-9 levels. These results contribute to our knowledge of the carrier proteins of an important functional glycan and the rate at which the glycan is displayed. This work also demonstrates a strategy for using the complementary methods of MS and antibody microarrays to identify protein carriers of glycans and assess the diagnostic value of measuring glycans on individual proteins.

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