Noninvasive diagnosis of liver cirrhosis using DNA sequencer–based total serum protein glycomics (original) (raw)

Nature Medicine volume 10, pages 429–434 (2004)Cite this article

Abstract

We applied our 'clinical glycomics' technology, based on DNA sequencer/fragment analyzers, to generate profiles of serum protein _N_-glycans of liver disease patients. This technology yielded a biomarker that distinguished compensated cirrhotic from noncirrhotic chronic liver disease patients, with 79% sensitivity and 86% specificity (100% sensitivity and specificity for decompensated cirrhosis). In combination with the clinical chemistry–based Fibrotest biomarker, compensated cirrhosis was detected with 100% specificity and 75% sensitivity. The current 'gold standard' for liver cirrhosis detection is an invasive, costly, often painful liver biopsy. Consequently, the highly specific set of biomarkers presented could obviate biopsy in many cirrhosis patients. This biomarker combination could eventually be used in follow-up examinations of chronic liver disease patients, to yield a warning that cirrhosis has developed and that the risk of complications (such as hepatocellular carcinoma) has increased considerably. Our clinical glycomics technique can easily be implemented in existing molecular diagnostics laboratories.

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Acknowledgements

N.C. is a postdoctoral fellow with the Fund for Scientific Research Flanders. This work was supported by the Fund for Scientific Research Flanders and by Ghent University (GOA Grant 12052299). The authors thank all blood donors for their participation; B. Vandekerckhove of the Blood Transfusion Center of the Red Cross Ghent and F. Dekeyser of the Department of Internal Medicine of Ghent University hospital for their collaboration; A. Vandeputte for expert technical assistance; A. Bredan for manuscript editing; B. Wuyts and J. Penders for assistance; M. Aebi for making an ABI 310 available for some of our experiments; and the management and technology transfer team of the Flanders Interuniversity Institute for Biotechnology for their encouragement.

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  1. Nico Callewaert
    Present address: Swiss Federal Institute of Technology (ETH), Schmelzbergstrasse 7, CH-8092, Zürich, Switzerland

Authors and Affiliations

  1. Department of Molecular Biomedical Research, Fundamental and Applied Molecular Biology, Ghent University and VIB, Technologiepark 927, Zwijnaarde, B-9052, Belgium
    Nico Callewaert, Annelies Van Hecke, Wouter Laroy & Roland Contreras
  2. Department of Gastroenterology and Hepatology, Ghent University Hospital, De Pintelaan 185, Ghent, B-9000, Belgium
    Hans Van Vlierberghe
  3. Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, Ghent, B-9000, Belgium
    Joris Delanghe

Authors

  1. Nico Callewaert
  2. Hans Van Vlierberghe
  3. Annelies Van Hecke
  4. Wouter Laroy
  5. Joris Delanghe
  6. Roland Contreras

Corresponding authors

Correspondence toNico Callewaert or Roland Contreras.

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There is a patent application (WO 03/087833) connected to this work.

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Callewaert, N., Vlierberghe, H., Hecke, A. et al. Noninvasive diagnosis of liver cirrhosis using DNA sequencer–based total serum protein glycomics.Nat Med 10, 429–434 (2004). https://doi.org/10.1038/nm1006

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