title: Identification of blood-protein carriers of the CA 19-9 antigen and characterization of prevalence in pancreatic diseases.
abstract: 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.
authors.affiliation: Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yue
authors.forename: Katie
authors.initials: K
authors.lastname: Partyka
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Maupin
authors.forename: Mary
authors.initials: M
authors.lastname: Hurley
authors.forename: Philip
authors.initials: P
authors.lastname: Andrews
authors.forename: Karen
authors.initials: K
authors.lastname: Kaul
authors.forename: A James
authors.initials: AJ
authors.lastname: Moser
authors.forename: Herbert
authors.initials: H
authors.lastname: Zeh
authors.forename: Randall E
authors.initials: RE
authors.lastname: Brand
authors.forename: Brian B
authors.initials: BB
authors.lastname: Haab
mesh_terms: D015415:Biomarkers / Q000737:chemistry; D018395:CA-19-9 Antigen / Q000097:blood* / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology*; D016022:Case-Control Studies; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry / Q000379:methods; D009077:Mucins / Q000097:blood / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000276:immunology; D010195:Pancreatitis / Q000097:blood / Q000276:immunology; D040081:Protein Array Analysis / Q000379:methods*; D040901:Proteomics / Q000379:methods; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D018395:CA-19-9 Antigen; D002352:Carrier Proteins; D009077:Mucins