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.