Evaluation of serum LINE-1 hypomethylation as a prognostic marker for hepatocellular carcinoma

Global hypomethylation is one of the most consistent epigenetic changes in cancer. Development of hepatocellular carcinoma (HCC) must be understood as a multistep process with accumulation of genetic and epigenetic alterations. In the last decades, in addition to genetic alterations, epigenetic changes have been recognized as an important and alternative mechanism in tumourigenesis. We investigated the clinical implications of global hypomethylation in the sera of patients with hepatocellular carcinoma (HCC). PCR was used to assess the methylation status of long interspersed nuclear element type 1 (LINE-1) repetitive sequences in genomic DNA derived from sera of 50 patients with HCC, 20 patients with cirrhosis, 20 patients with chronic hepatitis C and 10 healthy subjects. Serum genome hypomethylation was significantly increased in patients with HCC ( p < 0.001). The levels of serum LINE-1 hypomethylation at initial presentation correlated significantly with tumour size, tumour number and alpha-foetoprotein level. Moreover high serum LINE-1 hypomethylation correlates significantly with poor survival. Serum LINE-1 hypomethylation may serve as a prognostic marker for patients with HCC.