Purpose: Cholangiocarcinoma (CCA) is a malignancy of the bile ducts. The purpose of this discovery study was to identify effective serum markers for surveillance of cholangiocarcinoma. Experimental design: Using a glycomic method, patients with CCA were determined to have increased levels of alpha-1,3 and alpha-1,6 linked fucosylated glycan. Proteomic analysis of the serum fucosylated proteome identified proteins such as alpha-2-macroglobulin, kininogen, hemopexin, fetuin-A, alpha-1 anti-trypsin, and ceruloplasmin as being hyperfucosylated in HCC. The levels of these glycoproteins in 109 patients with CCA, primary sclerosing cholangitis (PSC), and control patients were compared to the performance of CA-19-9, the current “gold standard” assay for cholangiocarcinoma. Results: Fucosylated Fetuin-A (fc-Fetuin-A) had the best ability to differentiate CCA from PSC, with an AUROC of 0.812 or 0.8665 at differentiating CCA from those with PSC or other liver disease. CA-19-9 had poor ability to differentiate PSC from cholangiocarcinoma (AUROC of 0.625). Conclusion and clinical relevance: Using glycomic and proteomic methods we identified a set of proteins that contain altered glycan in the sera of those with CCA. One of these proteins, fucosylated Fetuin-A may have value in the surveillance of people at risk for the development of cholangiocarcinoma.
Bibliographical noteFunding Information:
This work was supported by grants R01 CA120206 (to ASM) and U01 CA168856 (to ASM) from the National Cancer Institute (NCI), the Hepatitis B Foundation, and an appropriation from The Commonwealth of Pennsylvania and also by grants CA100882 and CA128633 from the National Cancer Institute, The Cholangiocarcinoma Foundation (to LRR) and the Mayo Clinic Center for Cell Signaling in Gastroenterology (NIDDK P30DK084567). Dr. Adrian M. Di Bisceglie, Department of Internal Medicine and Saint Louis University Liver Center, Saint Louis University School of Medicine, St Louis, MO is thanked for providing samples.
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