Serum LINE-1 hypomethylation as a potential prognostic marker for hepatocellular carcinoma.

BACKGROUND We investigated the clinical implications of global hypomethylation, one of the most consistent epigenetic changes in cancer, in the sera of patients with hepatocellular carcinoma (HCC). METHODS Combined bisulfite restriction analysis PCR was used to assess the methylation status of LINE-1 repetitive sequences in genomic DNA derived from sera of 85 patients with HCC, 73 patients with cirrhosis, 20 healthy carriers of hepatitis B virus (HBV) and 30 healthy controls. RESULTS Serum genome hypomethylation, the percentage of unmethylated LINE-1, was significantly increased in patients with HCC (P<0.001). The levels of serum LINE-1 hypomethylation at initial presentation correlated significantly with the presence of HBsAg, large tumor sizes, and advanced tumor stages classified by the CLIP score. Multivariate analyses showed that serum LINE-1 hypomethylation was a significant and independent prognostic factor of overall survival. CONCLUSION Serum LINE-1 hypomethylation may serve as a prognostic marker for patients with HCC.

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