title: Analysis of serum haptoglobin fucosylation in hepatocellular carcinoma and liver cirrhosis of different etiologies.
abstract: We have developed herein a quantitative mass spectrometry-based approach to analyze the etiology-related alterations in fucosylation degree of serum haptoglobin in patients with liver cirrhosis and hepatocellular carcinoma (HCC). The three most common etiologies, including infection with hepatitis B virus (HBV), infection with hepatitis C virus (HCV), and heavy alcohol consumption (ALC), were investigated. Only 10 μL of serum was used in this assay in which haptoglobin was immunoprecipitated using a monoclonal antibody. The N-glycans of haptoglobin were released with PNGase F, desialylated, and permethylated prior to MALDI-QIT-TOF MS analysis. In total, N-glycan profiles derived from 104 individual patient samples were quantified (14 healthy controls, 40 cirrhosis, and 50 HCCs). A unique pattern of bifucosylated tetra-antennary glycan, with both core and antennary fucosylation, was identified in HCC patients. Quantitative analysis indicated that the increased fucosylation degree was highly associated with HBV- and ALC-related HCC patients compared to that of the corresponding cirrhosis patients. Notably, the bifucosylation degree was distinctly increased in HCC patients versus that in cirrhosis of all etiologies. The elevated bifucosylation degree of haptoglobin can discriminate early stage HCC patients from cirrhosis in each etiologic category, which may be used to provide a potential marker for early detection and to predict HCC in patients with cirrhosis.
authors.affiliation: Department of Surgery, University of Michigan Medical Center , Ann Arbor, Michigan 48109, United States.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhu
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Lin
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Haidi
authors.initials: H
authors.lastname: Yin
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: D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000097:blood*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D055088:Early Detection of Cancer; D005260:Female; D005643:Fucose / Q000378:metabolism*; D006031:Glycosylation; D006242:Haptoglobins / Q000378:metabolism*; D006509:Hepatitis B / Q000097:blood / Q000150:complications; D006526:Hepatitis C / Q000097:blood / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational
chemical_list: D014408:Biomarkers, Tumor; C485359:HP protein, human; D006242:Haptoglobins; D005643:Fucose