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

Meng Fang UGent, Sylviane Dewaele UGent, Yun-peng Zhao, Peter Starkel, Valerie Vanhooren UGent, Yue-ming Chen, Xin Ji, Ming Luo, Bao-mu Sun and Yves Horsmans, et al. (2010) MOLECULAR CANCER. 9.
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-a-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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ALPHA-GAL EPITOPE, LIVER FIBROSIS, HEPATITIS-B-VIRUS, FUCOSYLATION, GLYCOSYLATION, CANCER, CORE FUCOSE, HEPATOMA-CELLS, MASS-SPECTROMETRY, PROTEIN GLYCOMICS
journal title
MOLECULAR CANCER
Mol. Cancer
volume
9
article_number
215
pages
15 pages
Web of Science type
Article
Web of Science id
000282460500001
JCR category
ONCOLOGY
JCR impact factor
3.779 (2010)
JCR rank
54/181 (2010)
JCR quartile
2 (2010)
ISSN
1476-4598
DOI
10.1186/1476-4598-9-215
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
1062718
handle
http://hdl.handle.net/1854/LU-1062718
date created
2010-10-22 13:19:51
date last changed
2012-06-26 14:32:10
@article{1062718,
  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 {\textlangle} 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-a-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.},
  articleno    = {215},
  author       = {Fang, Meng and Dewaele, Sylviane and Zhao, Yun-peng and Starkel, Peter and Vanhooren, Valerie and Chen, Yue-ming and Ji, Xin and Luo, Ming and Sun, Bao-mu and Horsmans, Yves and Dell, Anne and Haslam, Stuart M and Grassi, Paola and Libert, Claude and Gao, Chun-fang and Chen, Cuiying},
  issn         = {1476-4598},
  journal      = {MOLECULAR CANCER},
  keyword      = {ALPHA-GAL EPITOPE,LIVER FIBROSIS,HEPATITIS-B-VIRUS,FUCOSYLATION,GLYCOSYLATION,CANCER,CORE FUCOSE,HEPATOMA-CELLS,MASS-SPECTROMETRY,PROTEIN GLYCOMICS},
  language     = {eng},
  pages        = {15},
  title        = {Serum N-glycome biomarker for monitoring development of DENA-induced hepatocellular carcinoma in rat},
  url          = {http://dx.doi.org/10.1186/1476-4598-9-215},
  volume       = {9},
  year         = {2010},
}

Chicago
Fang, Meng, Sylviane Dewaele, Yun-peng Zhao, Peter Starkel, Valerie Vanhooren, Yue-ming Chen, Xin Ji, et al. 2010. “Serum N-glycome Biomarker for Monitoring Development of DENA-induced Hepatocellular Carcinoma in Rat.” Molecular Cancer 9.
APA
Fang, M., Dewaele, S., Zhao, Y., Starkel, P., Vanhooren, V., Chen, Y., Ji, X., et al. (2010). Serum N-glycome biomarker for monitoring development of DENA-induced hepatocellular carcinoma in rat. MOLECULAR CANCER, 9.
Vancouver
1.
Fang M, Dewaele S, Zhao Y, Starkel P, Vanhooren V, Chen Y, et al. Serum N-glycome biomarker for monitoring development of DENA-induced hepatocellular carcinoma in rat. MOLECULAR CANCER. 2010;9.
MLA
Fang, Meng, Sylviane Dewaele, Yun-peng Zhao, et al. “Serum N-glycome Biomarker for Monitoring Development of DENA-induced Hepatocellular Carcinoma in Rat.” MOLECULAR CANCER 9 (2010): n. pag. Print.