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

综合分析LINE-1低甲基化水平，旨在开发食管癌新疗法

• 批准号: 23689061
• 负责人: BABA Yoshifumi
• 金额: $ 16.72万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23689061/
• 关键词: LINE-1; メチル化; 予後因子; エピジェネティクス; 食道癌; Pyrosequence; pyrosequence

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.

使用超过200个ESCC标本，我们利用亚硫酸氢盐焦磷酸测序技术定量LINE-1甲基化。LINE-1低甲基化在食管鳞癌中与较短的生存期相关，因此表明它有可能用作预后生物标志物。CGH阵列结果显示，LINE-1-低甲基化肿瘤在含有候选癌基因（如CDK 6）的各种基因座处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，与CDK 6阴性表达的患者相比，CDK 6阳性表达的患者的临床结局更差，这支持了CDK 6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被CDK 6表达减弱。LINE-1的低甲基化可能通过癌基因如CDK 6的基因组获得而导致ESCC的侵袭性肿瘤行为。

项目成果

上部消化管癌におけるLINE-1メチル化レベルのprognostic markerとしての意義

LINE-1甲基化水平作为上消化道癌预后标志物的意义

• 发表时间: 2012
• 作者: Chen F;Fujinaga T;Shoji T;Kubo T;Sonobe M;Sato M;Aoyama A;Sato T;Sakai H;Bando T;Date H;馬場 祥史
• 通讯作者: 馬場 祥史

Prognostic significance of LINE-1 methylation level in esophageal squamous cell carcinoma.

• DOI: 10.1200/jco.2012.30.4_suppl.26
• 发表时间: 2012-02
• 期刊: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
• 作者: Y. Baba;S. Iwagami;Masayuki Watanabe;H. Shigaki;S. Ida;Y. Nagai;T. Ishimoto;M. Iwatsuki;Y. Sakamoto;Y. Miyamoto;H. Baba

Prognostic significance of LINE-1 methylation level

LINE-1甲基化水平的预后意义

• 发表时间: 2012
• 作者: Nakajima D;Chen F;Okita K;Motoyama H;Hijiya K;Ohsumi A;Sakamoto J;Yamada T;Sato M;Aoyama A;Bando T;Date H.;馬場祥史;八木洋;馬場 祥史
• 通讯作者: 馬場 祥史

食道癌におけるLINE-1メチル化レベル-Prognosis and Epigenetic Field Defect-

食管癌中的 LINE-1 甲基化水平 -预后和表观遗传领域缺陷 -

• 发表时间: 2012
• 作者: Ohsumi A;Chen F;Sakamoto J;Nakajima D;Hijiya K;Motoyama H;Okita K;Horita K;Kikuchi R;Kojima F;Sato T;Yamada T;Sakai H;Bando T;Date H;馬場 祥史
• 通讯作者: 馬場 祥史

LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis.

• DOI: 10.1007/s10120-012-0209-7
• 发表时间: 2013-10
• 期刊: GASTRIC CANCER
• 影响因子: 7.4
• 作者: Shigaki, Hironobu;Baba, Yoshifumi;Watanabe, Masayuki;Murata, Asuka;Iwagami, Shiro;Miyake, Keisuke;Ishimoto, Takatsugu;Iwatsuki, Masaaki;Baba, Hideo
• 通讯作者: Baba, Hideo