title: Glycans related to the CA19-9 antigen are elevated in distinct subsets of pancreatic cancers and improve diagnostic accuracy over CA19-9.
abstract: OBJECTIVE
  The CA19-9 antigen is the current best biomarker for pancreatic cancer, but it is not elevated in about 25% of pancreatic cancer patients at a cutoff that gives a 25% false-positive rate. We hypothesized that antigens related to the CA19-9 antigen, which is a glycan called sialyl-Lewis A (sLeA), are elevated in distinct subsets of pancreatic cancers.
  
  
  METHODS
  We profiled the levels of multiple glycans and mucin glycoforms in plasma from 200 subjects with either pancreatic cancer or benign pancreatic disease, and we validated selected findings in additional cohorts of 116 and 100 subjects, the latter run blinded and including cancers that exclusively were early-stage.
  
  
  RESULTS
  We found significant elevations in two glycans: an isomer of sLeA called sialyl-Lewis X, present both in sulfated and non-sulfated forms; and the sialylated form of a marker for pluripotent stem cells, type 1 N-acetyl-lactosamine. The glycans performed as well as sLeA as individual markers and were elevated in distinct groups of patients, resulting in a 3-marker panel that significantly improved upon any individual biomarker. The panel gave 85% sensitivity and 90% specificity in the combined discovery and validation cohorts, relative to 54% sensitivity and 86% specificity for sLeA; and it gave 80% sensitivity and 84% specificity in the independent test cohort, as opposed to 66% sensitivity and 72% specificity for sLeA.
  
  
  CONCLUSIONS
  Glycans related to sLeA are elevated in distinct subsets of pancreatic cancers and yield improved diagnostic accuracy over CA19-9.
authors.affiliation: Van Andel Research Institute, Grand Rapids, MI.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Tang
authors.affiliation: Van Andel Research Institute, Grand Rapids, MI.
authors.forename: Katie
authors.initials: K
authors.lastname: Partyka
authors.affiliation: Van Andel Research Institute, Grand Rapids, MI.
authors.forename: Peter
authors.initials: P
authors.lastname: Hsueh
authors.affiliation: Van Andel Research Institute, Grand Rapids, MI.
authors.forename: Jessica Y
authors.initials: JY
authors.lastname: Sinha
authors.affiliation: Protein Metrics, Inc., San Carlos, CA.
authors.forename: Doron
authors.initials: D
authors.lastname: Kletter
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Herbert
authors.initials: H
authors.lastname: Zeh
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Randall E
authors.initials: RE
authors.lastname: Brand
authors.affiliation: Van Andel Research Institute, Grand Rapids, MI.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Haab
keywords: Biomarkers; antibody arrays; lectins; sialyl-Lewis A