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GlycoHepatoTest: validation and analytical technology development for implementation on microfluidics analyzers

Dieter Vanderschaeghe UGent (2010)
abstract
Glycomics research has become a versatile approach to several scientific problems, interfacing multiple disciplines. Profiling the N-glycans derived from total serum protein (N-glycome) has led to the discovery of a biomarker panel, renamed GlycoHepatoTest. The three biomarkers might be valuable over the complete spectrum of chronic liver disease: (i) monitoring liver fibrosis progression (GlycoFibroTest), (ii) diagnosis of early-stage cirrhosis to identify the patients that are at risk to develop decompensated cirrhosis and hepatocellular carcinoma (GlycoCirrhoTest), and (iii) GlycoHCCTest complements α-fetoprotein in the diagnosis of liver cancer in decompensated cirrhosis patients chronically infected with the hepatitis B virus. This novel panel has the potential to, in contrast to the invasive and costly liver biopsy, frequently obtain clinical relevant information during the course of these often long-term chronic conditions. However, the sample preparation protocol in its current format was not suitable for clinical implementation. Moreover, additional well-designed validation studies are required to demonstrate the clinical use and to further elucidate the correlation between N-glycome dynamics and the pathophysiology of chronic liver disease. Therefore, we designed an assay allowing the preparation of glycan samples within three hours that could be analyzed on capillary electrophoresis-based microfluidics platforms. Moreover, we could successfully validate GlycoFibroTest in a multicenter study consisting of 376 chronic hepatitis C patients. Interestingly, we discovered that undergalactosylated N-glycans, exponentially increasing with fibrosis stage, were exclusively present on Immunoglobulin G. This feature is a hallmark of chronic necro-inflammatory diseases, making it an intriguing research question for the future. We further investigated whether N-glycan profiling of the liver produced hemopexin contained information that could not be retrieved from the serum N-glycome profile. Initial results showed that the glycosylation changes on this protein improved the diagnosis of hepatocellular carcinoma in cirrhosis patients chronically infected with the hepatitis C virus. Finally, we examined an old observation that serum antibodies of chronic liver disease patients migrate differently during electrophoresis. We were able to conclude that these electrophoretic migration differences of antibodies correlate with their degree of sialylation. In this way, we could differentiate between healthy individuals and chronic liver disease patients.
Please use this url to cite or link to this publication:
author
promoter
UGent and UGent
organization
year
type
dissertation (monograph)
subject
pages
V, 217 pages
publisher
Ghent University. Faculty of Medicine and Health Sciences
place of publication
Ghent, Belgium
defense location
Zwijnaarde : Technologiepark (FSVM building)
defense date
2010-06-01 17:30
language
English
UGent publication?
yes
classification
D1
additional info
dissertation consists of copyrighted materials
copyright statement
I have transferred the copyright for this publication to the publisher
id
1094220
handle
http://hdl.handle.net/1854/LU-1094220
date created
2011-01-05 08:45:22
date last changed
2011-01-12 15:27:54
@phdthesis{1094220,
  abstract     = {Glycomics research has become a versatile approach to several scientific problems, interfacing multiple disciplines. Profiling the N-glycans derived from total serum protein (N-glycome) has led to the discovery of a biomarker panel, renamed GlycoHepatoTest. The three biomarkers might be valuable over the complete spectrum of chronic liver disease: (i) monitoring liver fibrosis progression (GlycoFibroTest), (ii) diagnosis of early-stage cirrhosis to identify the patients that are at risk to develop decompensated cirrhosis and hepatocellular carcinoma (GlycoCirrhoTest), and (iii) GlycoHCCTest complements \ensuremath{\alpha}-fetoprotein in the diagnosis of liver cancer in decompensated cirrhosis patients chronically infected with the hepatitis B virus. This novel panel has the potential to, in contrast to the invasive and costly
liver biopsy, frequently obtain clinical relevant information during the course of these often long-term chronic conditions. However, the sample preparation protocol in its current format
was not suitable for clinical implementation. Moreover, additional well-designed validation studies are required to demonstrate the clinical use and to further elucidate the correlation between N-glycome dynamics and the pathophysiology of chronic liver disease. Therefore, we designed an assay allowing the preparation of glycan samples within three hours that could be analyzed on capillary electrophoresis-based microfluidics platforms. Moreover, we could successfully validate GlycoFibroTest in a multicenter study consisting of 376 chronic hepatitis C patients. Interestingly, we discovered that undergalactosylated N-glycans, exponentially increasing with fibrosis stage, were exclusively present on Immunoglobulin G. This feature is a hallmark of chronic necro-inflammatory diseases, making it an intriguing research question for the future. We further investigated whether N-glycan profiling of the liver produced hemopexin contained information that could not be retrieved from the serum N-glycome profile. Initial results showed that the glycosylation changes on this protein improved the diagnosis of hepatocellular carcinoma in cirrhosis patients chronically infected with the hepatitis C virus. Finally, we examined an old observation that serum antibodies of chronic liver disease patients migrate differently during electrophoresis. We were able to conclude that these electrophoretic migration differences of antibodies correlate with their degree of sialylation. In this way, we could differentiate between healthy individuals and chronic liver disease patients.},
  author       = {Vanderschaeghe, Dieter},
  language     = {eng},
  pages        = {V, 217},
  publisher    = {Ghent University. Faculty of Medicine and Health Sciences},
  school       = {Ghent University},
  title        = {GlycoHepatoTest: validation and analytical technology development for implementation on microfluidics analyzers},
  year         = {2010},
}

Chicago
Vanderschaeghe, Dieter. 2010. “GlycoHepatoTest: Validation and Analytical Technology Development for Implementation on Microfluidics Analyzers”. Ghent, Belgium: Ghent University. Faculty of Medicine and Health Sciences.
APA
Vanderschaeghe, D. (2010). GlycoHepatoTest: validation and analytical technology development for implementation on microfluidics analyzers. Ghent University. Faculty of Medicine and Health Sciences, Ghent, Belgium.
Vancouver
1.
Vanderschaeghe D. GlycoHepatoTest: validation and analytical technology development for implementation on microfluidics analyzers. [Ghent, Belgium]: Ghent University. Faculty of Medicine and Health Sciences; 2010.
MLA
Vanderschaeghe, Dieter. “GlycoHepatoTest: Validation and Analytical Technology Development for Implementation on Microfluidics Analyzers.” 2010 : n. pag. Print.