Long interspersed nuclear element-1 hypomethylation is associated with poor outcomes via the activation of ST18 in human hepatocellular carcinoma

Abstract

The level of long interspersed nuclear element-1 (LINE-1) methylation, representing the global deoxyribonucleic acid methylation level, could contribute to the prognosis of cancer via the activation of oncogenes. This study was performed to evaluate the prognostic implications of LINE-1 hypomethylation in patients with hepatocellular carcinoma (HCC) and the possible mechanisms related to oncogene activation.Seventy-seven HCC patients between October 2014 and September 2015 were enrolled in this prospective study. Quantitative pyrosequencing was performed to assess the LINE-1 methylation level of HCC and matched non-HCC tissue samples. The expression of suppression of tumorigenicity 18 was measured by immunohistochemistry and its correlation with LINE-1 methylation levels was examined.LINE-1 was significantly hypomethylated in the HCC tissue compared with the matched nontumor tissue (64.0 ± 11.6% vs 75.6 ± 4.0%, P < .001). LINE-1 hypomethylation was an independent risk factor for overall survival (hazard ratio = 27.291, P = .032) and disease progression (hazard ratio = 5.298, P = .005). The expression of suppression of tumorigenicity 18 was higher in the hypomethylated LINE-1 HCC tissue than the hypermethylated LINE-1 tumor tissue (P = .030).LINE-1 hypomethylation may serve as a potential prognostic marker for patients with HCC.