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

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.

Automated summary

In patients with hepatocellular carcinoma (HCC), LINE-1 hypomethylation was found to be an independent risk factor for poor prognosis, potentially influencing tumor development by activating oncogenes. Additionally, the expression of suppression of tumorigenicity 18 was correlated with LINE-1 methylation levels and may play a role in the development of HCC.