Alteration of N-glycome in diethylnitrosamine-induced hepatocellular carcinoma mice: a non-invasive monitoring tool for liver cancer.
OBJECTIVE
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.
Liu
Xue-en
XE
Department of Microbiology, Peking University Health Science Center, Beijing, China.
Dewaele
Sylviane
S
Vanhooren
Valerie
V
Fan
Ye-Dong
YD
Wang
Ling
L
Van Huysse
Jacques
J
Zhuang
Hui
H
Contreras
Roland
R
Libert
Claude
C
Chen
Cuiying Chitty
CC
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004052:Diethylnitrosamine / Q000633:toxicity; D004586:Electrophoresis / Q000379:methods; D005647:Fucosyltransferases / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D011134:Polysaccharides / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D017931:DNA Primers; D018076:DNA, Complementary; D011134:Polysaccharides; D004052:Diethylnitrosamine; D005647:Fucosyltransferases; D017351:N-Acetylglucosaminyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase