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

Overview
Specialty Gastroenterology
Date 2016 Mar 22
PMID 26998508
Citations 25
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Abstract

Background And Aims: 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.

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References
1.
Andrews P, Banting G, Damjanov I, Arnaud D, Avner P . Three monoclonal antibodies defining distinct differentiation antigens associated with different high molecular weight polypeptides on the surface of human embryonal carcinoma cells. Hybridoma. 1984; 3(4):347-61. DOI: 10.1089/hyb.1984.3.347. View

2.
Fallon B, Curnutte B, Maupin K, Partyka K, Choi S, Brand R . The Marker State Space (MSS) method for classifying clinical samples. PLoS One. 2013; 8(6):e65905. PMC: 3672150. DOI: 10.1371/journal.pone.0065905. View

3.
Goonetilleke K, Siriwardena A . Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol. 2006; 33(3):266-70. DOI: 10.1016/j.ejso.2006.10.004. View

4.
Morris 4th J, Cano D, Sekine S, Wang S, Hebrok M . Beta-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice. J Clin Invest. 2010; 120(2):508-20. PMC: 2810083. DOI: 10.1172/JCI40045. View

5.
Yue T, Goldstein I, Hollingsworth M, Kaul K, Brand R, Haab B . The prevalence and nature of glycan alterations on specific proteins in pancreatic cancer patients revealed using antibody-lectin sandwich arrays. Mol Cell Proteomics. 2009; 8(7):1697-707. PMC: 2709194. DOI: 10.1074/mcp.M900135-MCP200. View