Glycans Related to the CA19-9 Antigen Are Increased in Distinct Subsets of Pancreatic Cancers and Improve Diagnostic Accuracy Over CA19-9

Huiyuan Tang, Katie Partyka, Peter Hsueh, Jessica Y. Sinha, Doron Kletter, Herbert Zeh, Ying Huang, Randall E. Brand, Brian B. Haab

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background & Aims: The cancer antigen 19-9 (CA19-9) is the current best biomarker for pancreatic cancer, but it is not increased in approximately 25% of pancreatic cancer patients at a cut-off value that provides 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 increased 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 with the investigators blinded to diagnoses and including cancers that exclusively were early stage. Results: We found significant increases in 2 glycans: an isomer of sLeA called sialyl-Lewis X, present both in sulfated and nonsulfated 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 increased in distinct groups of patients, resulting in a 3-marker panel that significantly improved upon any individual biomarker. The panel showed 85% sensitivity and 90% specificity in the combined discovery and validation cohorts, relative to 54% sensitivity and 86% specificity for sLeA; and it showed 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 increased in distinct subsets of pancreatic cancers and yield improved diagnostic accuracy compared with CA19-9.

Original languageEnglish (US)
Pages (from-to)210-221.e15
JournalCMGH
Volume2
Issue number2
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Fingerprint

Pancreatic Neoplasms
Polysaccharides
Antigens
Sensitivity and Specificity
Neoplasms
Biomarkers
Pancreatic Diseases
Pluripotent Stem Cells
Mucins
Research Personnel

Keywords

  • Antibody Arrays
  • Biomarkers
  • Lectins
  • Sialyl-Lewis A

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Glycans Related to the CA19-9 Antigen Are Increased in Distinct Subsets of Pancreatic Cancers and Improve Diagnostic Accuracy Over CA19-9. / Tang, Huiyuan; Partyka, Katie; Hsueh, Peter; Sinha, Jessica Y.; Kletter, Doron; Zeh, Herbert; Huang, Ying; Brand, Randall E.; Haab, Brian B.

In: CMGH, Vol. 2, No. 2, 01.02.2016, p. 210-221.e15.

Research output: Contribution to journalArticle

Tang, H, Partyka, K, Hsueh, P, Sinha, JY, Kletter, D, Zeh, H, Huang, Y, Brand, RE & Haab, BB 2016, 'Glycans Related to the CA19-9 Antigen Are Increased in Distinct Subsets of Pancreatic Cancers and Improve Diagnostic Accuracy Over CA19-9', CMGH, vol. 2, no. 2, pp. 210-221.e15. https://doi.org/10.1016/j.jcmgh.2015.12.003
Tang, Huiyuan ; Partyka, Katie ; Hsueh, Peter ; Sinha, Jessica Y. ; Kletter, Doron ; Zeh, Herbert ; Huang, Ying ; Brand, Randall E. ; Haab, Brian B. / Glycans Related to the CA19-9 Antigen Are Increased in Distinct Subsets of Pancreatic Cancers and Improve Diagnostic Accuracy Over CA19-9. In: CMGH. 2016 ; Vol. 2, No. 2. pp. 210-221.e15.
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abstract = "Background & Aims: The cancer antigen 19-9 (CA19-9) is the current best biomarker for pancreatic cancer, but it is not increased in approximately 25{\%} of pancreatic cancer patients at a cut-off value that provides 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 increased 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 with the investigators blinded to diagnoses and including cancers that exclusively were early stage. Results: We found significant increases in 2 glycans: an isomer of sLeA called sialyl-Lewis X, present both in sulfated and nonsulfated 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 increased in distinct groups of patients, resulting in a 3-marker panel that significantly improved upon any individual biomarker. The panel showed 85{\%} sensitivity and 90{\%} specificity in the combined discovery and validation cohorts, relative to 54{\%} sensitivity and 86{\%} specificity for sLeA; and it showed 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 increased in distinct subsets of pancreatic cancers and yield improved diagnostic accuracy compared with CA19-9.",
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T1 - Glycans Related to the CA19-9 Antigen Are Increased in Distinct Subsets of Pancreatic Cancers and Improve Diagnostic Accuracy Over CA19-9

AU - Tang, Huiyuan

AU - Partyka, Katie

AU - Hsueh, Peter

AU - Sinha, Jessica Y.

AU - Kletter, Doron

AU - Zeh, Herbert

AU - Huang, Ying

AU - Brand, Randall E.

AU - Haab, Brian B.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Background & Aims: The cancer antigen 19-9 (CA19-9) is the current best biomarker for pancreatic cancer, but it is not increased in approximately 25% of pancreatic cancer patients at a cut-off value that provides 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 increased 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 with the investigators blinded to diagnoses and including cancers that exclusively were early stage. Results: We found significant increases in 2 glycans: an isomer of sLeA called sialyl-Lewis X, present both in sulfated and nonsulfated 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 increased in distinct groups of patients, resulting in a 3-marker panel that significantly improved upon any individual biomarker. The panel showed 85% sensitivity and 90% specificity in the combined discovery and validation cohorts, relative to 54% sensitivity and 86% specificity for sLeA; and it showed 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 increased in distinct subsets of pancreatic cancers and yield improved diagnostic accuracy compared with CA19-9.

AB - Background & Aims: The cancer antigen 19-9 (CA19-9) is the current best biomarker for pancreatic cancer, but it is not increased in approximately 25% of pancreatic cancer patients at a cut-off value that provides 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 increased 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 with the investigators blinded to diagnoses and including cancers that exclusively were early stage. Results: We found significant increases in 2 glycans: an isomer of sLeA called sialyl-Lewis X, present both in sulfated and nonsulfated 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 increased in distinct groups of patients, resulting in a 3-marker panel that significantly improved upon any individual biomarker. The panel showed 85% sensitivity and 90% specificity in the combined discovery and validation cohorts, relative to 54% sensitivity and 86% specificity for sLeA; and it showed 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 increased in distinct subsets of pancreatic cancers and yield improved diagnostic accuracy compared with CA19-9.

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KW - Biomarkers

KW - Lectins

KW - Sialyl-Lewis A

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