Comprehensive analysis of LINE-1 hypomethylation level aimed at the development of new treatments for esophageal cancer

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Using more than 200 ESCC specimens,we quantified the LINE-1 methylation by utilizing the bisulfite pyrosequencing technology. LINE-1 hypomethylation in ESCC is associated with a shorter survival, thus suggesting that it has potential for use as a prognostic biomarker. Result of CGH array, LINE-1-hypomethylated tumors showed highly frequent genomic gains at various loci containing candidate oncogenes such as CDK6. In our cohort of 129 patients with ESCC, cases with CDK6-positive expression experienced worse clinical outcome compared with those with CDK6-negative expression, supporting the oncogenic role of CDK6 in ESCC. In addition, we found that the prognostic impact of LINE-1 hypomethylation might be attenuated by CDK6 expression. LINE-1 hypomethylation in ESCC might contribute to the acquisition of aggressive tumor behavior through genomic gains of oncogenes such as CDK6.