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

利用200多个食管癌标本，我们利用亚硫酸氢盐焦磷酸测序技术对LINE-1甲基化进行了量化。食管鳞癌中Line-1低甲基化与较短的生存期有关，因此，它有可能被用作预后生物标记物。CGH芯片结果显示，LINE-1-低甲基化肿瘤在包含CDK6等候选癌基因的多个基因座上显示出高频率的基因组获得。在我们的129例ESCC患者中，CDK6阳性表达的患者与CDK6阴性表达的患者相比，临床结果更差，这支持了CDK6在ESCC中的致癌作用。此外，我们发现CDK6的表达可能会减弱LINE-1低甲基化对预后的影响。食管鳞癌中LINE-1的低甲基化可能通过CDK6等癌基因的基因组获得而有助于获得侵袭性的肿瘤行为。

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.