Abstract :
Purpose: Global hypomethylation is one of the most consistent epigenetic changes in hepatocellular
carcinoma (HCC), and may play crucial roles in multistage hepatocarcinogenesis. However, the clinical implications of this epigenetic alteration in sera of patients with HCC have not been investigated.
Experimental Designs: The combined bisulfite restriction analysis PCR was applied to assess the
methylation status of LINE-1 repetitive sequences in genomic DNA derived from serum samples of 85 patients with HCC, 73 patients with cirrhosis, and 20 healthy carriers of hepatitis B.
Results: Serum LINE-1 hypomethylation was found to be significantly elevated in patients with HCC
(mean 53.17 +/- 7.74%) compared to those of healthy carriers (48.07 +/- 6.20%), and cirrhosis (48.78 +/- 8.01%) (P = 0.003 and P = 0.001, respectively). There was no significant difference in serum LINE-1 hypomethylation level between non-HCC individuals. The levels of serum LINE-1 hypomethylation at initial presentation correlated significantly with presence of HBsAg, a large tumor size, and advanced tumor stages classified by the CLIP score.
Conclusions: Significant correlations of serum LINE-1 hypomethylation levels with tumor size and
tumor stage suggest that global hypomethylation may play important roles in promoting tumor progression and invasiveness. These findings indicate that serum LINE-1 hypomethylation may be served as a molecular marker for predicting the prognosis of patients with HCC.
[Thai J Gastroenterol 2007; 8(1): 12-18] |
file/Thai-Journal-of-gastroenterology-vol-8-no-1-1309226.pdf