Abstract:

Objective To study the potential association between liver cancer and methylation of the promoters of the genes DLC1，ASC，p16，and DLK1. Methods Primary hepatocellular carcinoma（PHC）was induced in 35 Wistar rats by injection of AFB₁. Another group of 20 rats received no drug and served as a negative control. At week 52，all rats were killed and tissue samples were harvested and analyzed for histopathology. Methylation-specific PCR was used to analyze methylation of the promoters of the genes DLC1，ASC，p16，and DLK1 in rat liver in both groups. Results AFB₁-induction of PHC led to the expected pathological changes in rat liver. Methylation rates of DLC1，ASC，p16 in liver tissue were significantly higher in rats with PHC（83.3%，93.3%，86.7%，respectively） than in control rats （14.3%，35.7%，21.4%；all P<0.05），whereas the opposite was true for methylation rates of DLK1 （10.0% vs 85.7%，P<0.05）. Conclusion PHC may be associated with upregulation of DLC1，ASC，and p16 methylation，as well as downregulation of DLK1 methylation. Thus，aberrant methylation of DLC1，ASC，p16 and DLK1 may contribute to PHC onset and progression.

Key words: Liver neoplasm, DLC1, ASC, p16, DLK1, Gege, Methylation