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.
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.
Authors: Timothy M Block; Mary Ann Comunale; Melissa Lowman; Laura F Steel; Patrick R Romano; Claus Fimmel; Bud C Tennant; W Thomas London; Alison A Evans; Baruch S Blumberg; Raymond A Dwek; Tajinder S Mattu; Anand S Mehta Journal: Proc Natl Acad Sci U S A Date: 2005-01-10 Impact factor: 11.205
Authors: Mary Ann Comunale; Lucy Rodemich-Betesh; Julie Hafner; Mengjun Wang; Pamela Norton; Adrian M Di Bisceglie; Timothy Block; Anand Mehta Journal: PLoS One Date: 2010-08-25 Impact factor: 3.240
Authors: Mengjun Wang; Ronald E Long; Mary Ann Comunale; Omer Junaidi; Jorge Marrero; Adrian M Di Bisceglie; Timothy M Block; Anand S Mehta Journal: Cancer Epidemiol Biomarkers Prev Date: 2009-05-19 Impact factor: 4.254
Authors: Anand S Mehta; Ronald E Long; Mary Ann Comunale; Mengjun Wang; Lucy Rodemich; Jonathan Krakover; Ramila Philip; Jorge A Marrero; Raymond A Dwek; Timothy M Block Journal: J Virol Date: 2007-11-28 Impact factor: 5.103
Authors: Tanya R McKitrick; Steffen M Bernard; Alexander J Noll; Bernard C Collins; Christoffer K Goth; Alyssa M McQuillan; Jamie Heimburg-Molinaro; Brantley R Herrin; Ian A Wilson; Max D Cooper; Richard D Cummings Journal: Commun Biol Date: 2021-06-03
Authors: Danielle A Scott; Mengjun Wang; Stephane Grauzam; Sarah Pippin; Alyson Black; Peggi M Angel; Richard R Drake; Stephen Castellino; Yuko Kono; Don C Rockey; Anand S Mehta Journal: Front Immunol Date: 2022-02-07 Impact factor: 8.786