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Mol Cell Proteomics. 2009 May;8(5):986-94. doi: 10.1074/mcp.M800470-MCP200. Epub 2009 Jan 29.

GlycoFibroTest is a highly performant liver fibrosis biomarker derived from DNA sequencer-based serum protein glycomics.

Author information

1
Unit for Molecular Glycobiology, Department for Molecular Biomedical Research, Flanders Institute for Biotechnology (VIB), Technologiepark 927, B-9052 Ghent, Belgium.

Abstract

Liver fibrosis is currently assessed by liver biopsy, a costly and rather cumbersome procedure that is unsuitable for frequent patient monitoring, which drives research into biomarkers for this purpose. To investigate whether the serum N-glycome contains information suitable for this goal, we developed a 96-well plate-based serum N-glycomics sample preparation protocol that only involves fluid transfer steps and incubations in a PCR thermocycler yielding 8-aminopyrene-1,3,6-trisulfonic acid-labeled N-glycans. These N-glycans are then ready for analysis on the capillary electrophoresis-based DNA sequencers that are the current standard in clinical genetics laboratories worldwide. Subsequently we performed a multicenter, blinded study of 376 consecutive chronic hepatitis C virus patients for which liver biopsies and extensive serum biochemistry data were available. Among patients, the METAVIR fibrosis stage distribution was as follows: 10.6% F0, 44.4% F1, 20.5% F2, 18.4% F3, and 6.1% F4. We found that the ratio of two N-glycans, here called GlycoFibroTest, correlates with the histological fibrosis stage equally well as FibroTest (rho = 0.4-0.5 in F1-F4), which is used in the clinic today. Finally using affinity chromatography we depleted sera of immunoglobulin G, and this resulted in a complete removal of the undergalactosylated biantennary glycans from the N-glycome, which are partially determining GlycoFibroTest.

PMID:
19181623
PMCID:
PMC2689777
DOI:
10.1074/mcp.M800470-MCP200
[Indexed for MEDLINE]
Free PMC Article

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