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

利用亚硫酸氢盐焦磷酸测序技术，对200多个ESCC标本进行了LINE-1甲基化定量分析。ESCC中LINE-1低甲基化与较短的生存期相关，因此表明它有潜力作为预后生物标志物。CGH阵列的结果显示，line -1低甲基化肿瘤在包含候选癌基因（如CDK6）的各种位点上显示出高度频繁的基因组增益。在我们的129例ESCC患者队列中，CDK6阳性表达的病例比CDK6阴性表达的病例的临床结果更差，这支持了CDK6在ESCC中的致癌作用。此外，我们发现LINE-1低甲基化的预后影响可能会被CDK6表达减弱。ESCC中的LINE-1低甲基化可能通过获得癌基因（如CDK6）的基因组来促进侵袭性肿瘤行为的获得。

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.