N-glycomic changes in hepatocellular carcinoma patients with liver cirrhosis induced by hepatitis B virus

Authors

  • Xue-En Liu,

    1. Department for Molecular Biomedical Research, Flanders Institute for Biotechnology, Ghent, Belgium
    2. Department of Molecular Biology, Ghent University, Ghent, Belgium
    3. Department of Microbiology, Peking University Health Science Center, Haidian District, Beijing, People's Republic of China
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    • These authors contributed equally to this study.

  • Liesbeth Desmyter,

    1. Department for Molecular Biomedical Research, Flanders Institute for Biotechnology, Ghent, Belgium
    2. Department of Molecular Biology, Ghent University, Ghent, Belgium
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    • These authors contributed equally to this study.

  • Chun-Fang Gao,

    1. Department of Laboratory Medicine, Second Military Medical University, Eastern Hepatobiliary Hospital, Shanghai, People's Republic of China
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  • Wouter Laroy,

    1. Department for Molecular Biomedical Research, Flanders Institute for Biotechnology, Ghent, Belgium
    2. Department of Molecular Biology, Ghent University, Ghent, Belgium
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  • Sylviane Dewaele,

    1. Department for Molecular Biomedical Research, Flanders Institute for Biotechnology, Ghent, Belgium
    2. Department of Molecular Biology, Ghent University, Ghent, Belgium
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  • Valerie Vanhooren,

    1. Department for Molecular Biomedical Research, Flanders Institute for Biotechnology, Ghent, Belgium
    2. Department of Molecular Biology, Ghent University, Ghent, Belgium
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  • Ling Wang,

    1. Department of Microbiology, Peking University Health Science Center, Haidian District, Beijing, People's Republic of China
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  • Hui Zhuang,

    1. Department of Microbiology, Peking University Health Science Center, Haidian District, Beijing, People's Republic of China
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  • Nico Callewaert,

    1. Department for Molecular Biomedical Research, Flanders Institute for Biotechnology, Ghent, Belgium
    2. Department of Biochemistry, Physiology and Microbiology, Ghent University, Ghent, Belgium
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  • Claude Libert,

    1. Department for Molecular Biomedical Research, Flanders Institute for Biotechnology, Ghent, Belgium
    2. Department of Molecular Biology, Ghent University, Ghent, Belgium
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  • Roland Contreras,

    1. Department for Molecular Biomedical Research, Flanders Institute for Biotechnology, Ghent, Belgium
    2. Department of Molecular Biology, Ghent University, Ghent, Belgium
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  • Cuiying Chen

    Corresponding author
    1. Department for Molecular Biomedical Research, Flanders Institute for Biotechnology, Ghent, Belgium
    2. Department of Molecular Biology, Ghent University, Ghent, Belgium
    • Department of Molecular Biomedical Research, Flanders Institute for Biotechnology and Department of Molecular Biology, Ghent University, Technologiepark 927, B-9052 Ghent, Belgium===

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  • Potential conflict of interest: Nothing to report.

Abstract

We evaluated the use of blood serum N-glycan fingerprinting as a tool for the diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis induced by hepatitis B virus (HBV). A group of 450 HBV-infected patients with liver fibrosis or cirrhosis with or without HCC were studied. HCC was diagnosed by α-fetoprotein (AFP) analysis, ultrasonography, and/or computed tomography and was studied histologically. N-glycan profiles of serum proteins were determined with DNA sequencer–based carbohydrate analytical profiling technology. In this study, we found that a branch alpha(1,3)-fucosylated triantennary glycan was more abundant in patients with HCC than in patients with cirrhosis, patients with fibrosis, and healthy blood donors, whereas a bisecting core alpha(1,6)-fucosylated biantennary glycan was elevated in patients with cirrhosis. The concentration of these 2 glycans and the log ratio of peak 9 to peak 7 (renamed the GlycoHCCTest) were associated with the tumor stage. Moreover, for screening patients with HCC from patients with cirrhosis, the overall sensitivity and specificity of the GlycoHCCTest were very similar to those of AFP. Conclusion: This study indicates that a branch alpha(1,3)-fucosylated glycan is associated with the development of HCC. The serum N-glycan profile is a promising noninvasive method for detecting HCC in patients with cirrhosis and could be a valuable supplement to AFP in the diagnosis of HCC in HBV-infected patients with liver cirrhosis. Its use for the screening, follow-up, and management of patients with cirrhosis and HCC should be evaluated further. (HEPATOLOGY 2007.)

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