title: Mass-selected site-specific core-fucosylation of ceruloplasmin in alcohol-related hepatocellular carcinoma.
abstract: A mass spectrometry-based methodology has been developed to study changes in core-fucosylation of serum ceruloplasmin that are site-specific between cirrhosis and hepatocellular carcinoma (HCC). The serum samples studied for these changes were from patients affected by cirrhosis or HCC with different etiologies, including alcohol, hepatitis B virus, or hepatitis C virus. The methods involved trypsin digestion of ceruloplasmin into peptides followed by Endo F3 digestion, which removed most of the glycan structure while retaining the innermost N-acetylglucosamine (GlcNAc) and/or core-fucose bound to the peptide. This procedure simplified the structures for further analysis by mass spectrometry, where four core-fucosylated sites (sites 138, 358, 397, and 762) were detected in ceruloplasmin. The core-fucosylation ratio of three of these sites increased significantly in alcohol-related HCC samples (sample size = 24) compared to that in alcohol-related cirrhosis samples (sample size = 18), with the highest AUC value of 0.838 at site 138. When combining the core-fucosylation ratio of site 138 in ceruloplasmin and the alpha-fetoprotein (AFP) value, the AUC value increased to 0.954 (ORsite138 = 12.26, p = 0.017; ORAFP = 3.64, p = 0.022), which was markedly improved compared to that of AFP (AUC = 0.867) (LR test p = 0.0002) alone. However, in HBV- or HCV-related liver diseases, no significant site-specific change in core-fucosylation of ceruloplasmin was observed between HCC and cirrhosis.
authors.affiliation: Department of Surgery, University of Michigan Medical Center , Ann Arbor, Michigan 48109, United States.
authors.forename: Haidi
authors.initials: H
authors.lastname: Yin
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Lin
authors.forename: Song
authors.initials: S
authors.lastname: Nie
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Zhijing
authors.initials: Z
authors.lastname: Tan
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhu
authors.forename: Jianliang
authors.initials: J
authors.lastname: Dai
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.forename: Jorge
authors.initials: J
authors.lastname: Marrero
authors.forename: David M
authors.initials: DM
authors.lastname: Lubman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects*; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000097:blood / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D016022:Case-Control Studies; D002570:Ceruloplasmin / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D006509:Hepatitis B / Q000097:blood / Q000150:complications; D006526:Hepatitis C / Q000097:blood / Q000150:complications; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D012372:ROC Curve; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D002570:Ceruloplasmin