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

Proteomics. 2011 Sep;11(18):3665-74. doi: 10.1002/pmic.201000827. Epub 2011 Aug 2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / chemistry
  • CA-19-9 Antigen / blood*
  • CA-19-9 Antigen / chemistry
  • Carrier Proteins / chemistry
  • Carrier Proteins / immunology*
  • Case-Control Studies
  • Humans
  • Immunoprecipitation
  • Mass Spectrometry / methods
  • Mucins / blood
  • Mucins / chemistry
  • Mucins / immunology
  • Mucins / isolation & purification*
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / immunology
  • Pancreatitis / blood
  • Pancreatitis / immunology
  • Protein Array Analysis / methods*
  • Proteomics / methods
  • Sensitivity and Specificity

Substances

  • Biomarkers
  • CA-19-9 Antigen
  • Carrier Proteins
  • Mucins