Alteration of N-glycome in diethylnitrosamine-induced hepatocellular carcinoma mice: a non-invasive monitoring tool for liver cancer.

Abstract

BACKGROUND AND AIMS:

There is a demand for serum markers that can routinely assess the progression of liver cancer. DENA (diethylnitrosamine), a hepatocarcinogen, is commonly used in an experimental mouse model to induce liver cancer that closely mimics a subclass of human hepatocellular carcinoma (HCC). However, blood monitoring of the progression of HCC in mouse model has not yet been achieved. In this report, we studied glycomics during the development of mouse HCC induced by DENA.

METHODS:

Mouse HCC was induced by DENA. Serum N-glycans were profiled using the sequencer assisted-Fluorophore-assisted carbohydrate electrophoresis technique developed in our laboratory. Possible alteration in the transcription of genes relevant to the synthesis of the changed glycans was analysed by real-time polymerase chain reaction.

RESULTS:

In comparison with the control mice that received the same volume of saline, a tri-antennary glycan (peak 8) and a biantennary glycan (peak 4) in serum total glycans of DENA mice increased gradually but significantly during progression of liver cancer, whereas a core-fucosylated biantennary glycan (peak 6) decreased. Expression of alpha-1,6-fucosyltransferase 8 (Fut8), which is responsible for core fucosylation, decreased in the liver of DENA mice compared with that of age-matched control mice. Likewise, the expression level of Mgat4a, which is responsible for tri-antennary, significantly increased in the liver of DENA mice (P<0.001).

CONCLUSIONS:

The changes of N-glycan levels in the serum could be used as a biomarker to monitor the progress of HCC and to follow up the treatment of liver tumours in this DENA mouse model.

• Authors: Xue-en Liu, Sylviane Dewaele, Valerie Vanhooren, Ye-Dong Fan, Ling Wang, Jacques Van Huysse, Hui Zhuang, Roland Contreras, Claude Libert, Cuiying Chitty Chen
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 30 Issue 8 Pg. 1221-8 (Sep 2010) ISSN: 1478-3231 [Electronic] United States
• PMID: 20524982 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• DNA Primers
• DNA, Complementary
• Polysaccharides
• Diethylnitrosamine
• Fucosyltransferases
• N-Acetylglucosaminyltransferases
• Glycoprotein 6-alpha-L-fucosyltransferase

Topics

• Animals
• Biomarkers, Tumor (blood)
• Carcinoma, Hepatocellular (chemically induced, diagnosis, metabolism)
• DNA Primers (genetics)
• DNA, Complementary (genetics)
• Diethylnitrosamine (toxicity)
• Electrophoresis (methods)
• Fucosyltransferases (metabolism)
• Liver (pathology)
• Liver Neoplasms, Experimental (chemically induced, diagnosis, metabolism)
• Mice
• N-Acetylglucosaminyltransferases (metabolism)
• Polysaccharides (blood, genetics)
• Reverse Transcriptase Polymerase Chain Reaction