Analysis of Serum Haptoglobin Fucosylation in Hepatocellular Carcinoma and Liver Cirrhosis of Different Etiologies

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...

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Bibliographic Details
Published in:Journal of proteome research Vol. 13; no. 6; pp. 2986 - 2997
Main Authors: Zhu, Jianhui, Lin, Zhenxin, Wu, Jing, Yin, Haidi, Dai, Jianliang, Feng, Ziding, Marrero, Jorge, Lubman, David M
Format: Journal Article
Language:English
Published: United States American Chemical Society 06.06.2014
Subjects:
Aged
Alcohol Drinking - adverse effects
Biomarkers, Tumor - blood
Carbohydrate Conformation
Carbohydrate Sequence
Carcinoma, Hepatocellular - blood
Carcinoma, Hepatocellular - diagnosis
Carcinoma, Hepatocellular - etiology
Case-Control Studies
Diagnosis, Differential
Early Detection of Cancer
Female
Fucose - metabolism
Glycosylation
Haptoglobins - metabolism
Hepatitis B - blood
Hepatitis B - complications
Hepatitis C - blood
Hepatitis C - complications
Humans
Liver Cirrhosis - blood
Liver Cirrhosis - diagnosis
Liver Cirrhosis - etiology
Liver Neoplasms - blood
Liver Neoplasms - diagnosis
Liver Neoplasms - etiology
Male
Middle Aged
Molecular Sequence Data
Protein Processing, Post-Translational
fucosylation
Hepatocellular carcinoma
biomarker
haptoglobin
MALDI
liver cirrhosis
ISSN:1535-3893, 1535-3907, 1535-3907
Online Access:Get full text
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Summary: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.
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ISSN:1535-3893
1535-3907
1535-3907
DOI:10.1021/pr500128t