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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

Serum N-glycome biomarker for monitoring development of DENA-induced hepatocellular carcinoma in rat

Authors: Meng Fang, Sylviane Dewaele, Yun-peng Zhao, Peter Stärkel, Valerie Vanhooren, Yue-ming Chen, Xin Ji, Ming Luo, Bao-mu Sun, Yves Horsmans, Anne Dell, Stuart M Haslam, Paola Grassi, Claude Libert, Chun-fang Gao, Cuiying Chitty Chen

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

There is a demand for serum markers for the routine assessment of the progression of liver cancer. We previously found that serum N-linked sugar chains are altered in hepatocellular carcinoma (HCC). Here, we studied glycomic alterations during development of HCC in a rat model.

Results

Rat HCC was induced by the hepatocarcinogen, diethylnitrosamine (DENA). N-glycans were profiled using the DSA-FACE technique developed in our laboratory.
In comparison with control rats, DENA rats showed a gradual but significant increase in two glycans (R5a and R5b) in serum total N-glycans during progression of liver cirrhosis and cancer, and a decrease in a biantennary glycan (P5). The log of the ratio of R5a to P1 (NGA2F) and R5b to P1 [log(R5a/P1) and log(R5b/P1)] were significantly (p < 0.0001) elevated in HCC rats, but not in rats with cirrhosis or fibrosis or in control rats. We thus propose a GlycoTest model using the above-mentioned serum glycan markers to monitor the progression of cirrhosis and HCC in the DENA-treated rat model. When DENA-treated rats were subsequently treated with farnesylthiosalicyclic acid, an anticancer drug, progression to HCC was prevented and GlycoTest markers (P5, R5a and R5b) reverted towards non-DENA levels, and the HCC-specific markers, log(R5a/P1) and log(R5b/P1), normalized completely. Conclusions: We found an increase in core-α-1,6-fucosylated glycoproteins in serum and liver of rats with HCC, which demonstrates that fucosylation is altered during progression of HCC. Our GlycoTest model can be used to monitor progression of HCC and to follow up treatment of liver tumors in the DENA rat. This GlycoTest model is particularly important because a rapid non-invasive diagnostic procedure for tumour progression in this rat model would greatly facilitate the search for anticancer drugs.
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Metadata
Title
Serum N-glycome biomarker for monitoring development of DENA-induced hepatocellular carcinoma in rat
Authors
Meng Fang
Sylviane Dewaele
Yun-peng Zhao
Peter Stärkel
Valerie Vanhooren
Yue-ming Chen
Xin Ji
Ming Luo
Bao-mu Sun
Yves Horsmans
Anne Dell
Stuart M Haslam
Paola Grassi
Claude Libert
Chun-fang Gao
Cuiying Chitty Chen
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-215

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