Research project BL/C/42 (Research action BL)
1/12/2007-30/11/2009
Context and objectives
Most serum N-linked glycoproteins are synthesized by the liver and by B-lymphocytes. Any changes in serum total N-glycans could reflect alteration of liver or B-lymphocyte physiology. Our previous studies in Chinese liver fibrotic group and HCC patients infected with HBV showed alterations in N-glycan profilings. This project is aimed at studying glycomics during progress of liver fibrosis and HCC and has major objectives:
To evaluate the usefulness of glycomics biomarker for diagnosis of liver fibrosis in follow up the drug treatment in Chinese patients with fibrosis or cirrhosis.
To evaluate the usefulness of our N-glycomics HCC marker for early detection of cancer; to evaluate the usefulness of glycomics marker in a follow-up the treatment with Chinese antitumor herbs and, or receiving chemotherapy.
To evaluate the usefulness of glycomics for pre-screening Chinese antifibrotic herbs and antitumor herbs (TCMs) in a rodent model and a HCC rodent model by comparing them to existing Western drugs.
Methodology
• The lab in Shanghai (EHBH), China, is responsible for the collection of the blood serum samples from the Chinese patients with fibrosis, cirrhosis or HCC, and the set-up of an extensive clinical data set for the subjects.
• The lab in Ghent University is responsible for the glycan profiling analysis of the blood serum samples from Chinese patients.
• An appropriate analysis of the clinical, biochemical data and N-glycome data is performed in the group in Ghent University.
• Glycomics study in rodent HCC model induced by diethylnitrosamine is carried out in China and Ghent.
Results
• We found that in HBV patients, like in HCV patients, several serum N-glycans were altered during development of liver fibrosis. We further confirmed glycome HCC biomarker in a large cohort of Chinese HCC patients.
• After the treatment in the fibrotic liver patients or HCC, the glycome biomarkers are reversed, respectively.
• The glycosylation alteration during liver cancer progress was observed in the DENA induced HCC mouse and rat. We propose a GlycoTest model using the serum glycan markers to monitor the progression of cirrhosis and HCC in the DENA induced HCC-rat.
