演題抄録

FACO International Workshop

開催概要
開催回
第53回・2015年・京都
 

UHRF1 overexpression is associated with LINE-1 hypomethylation and poorer patient outcome in esophageal squamous cell carcinoma

演題番号 : FWS8-1

[筆頭演者]
Nakamura Kenichi:1 
[共同演者]
Baba Yoshifumi:1、Kosumi Keisuke:1、Miyake Keisuke:1、Harada Kazuto:1、Ohuchi Mayuko:1、Kurashige Junji:1、Iwatsuki Masaaki:1、Miyamoto Yuji:1、Sakamoto Yasuo:1、Yoshida Naoya:1、Baba Hideo:1

1:Gastroenterological Surgery, Graduate School, Kumamoto University

 

Background: Global DNA hypomethylation has been shown to occur in many cancers, and Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an important key regulator of DNA methylation. Several studies have reported that UHRF1 overexpression caused global DNA hypomethylation and was associated with poorer patient outcome in various cancers. Long interspersed nucleotide element 1 (LINE-1), constituting a substantial portion of the human genome, is regarded to be a good indicator of the global DNA methylation, and we have reported the utility of LINE-1 methylation level as a prognostic biomarker in esophageal squamous cell carcinoma (ESCC). However, the relationship between UHRF1 and LINE-1 methylation levels in ESCC remains still unclear.
Methods: Using 16 frozen tissues (matched pairs of cancer and normal epithelium), and 160 curatively resected esophageal cancer specimens, we analyzed the relationship between UHRF1 expression, LINE-1 methylation levels and patient outcome. We measured UHRF1 expression by real-time PCR and immunohistochemistry, and LINE-1 methylation levels by bisulfite- pyrosequencing technology.
Results: In 16 pairs of frozen tissues, UHRF1 mRNA expression in cancer was significantly higher than in normal epithelium (P<0.0001), and it was negatively associated with LINE-1 methylation levels (P=0.0044). Additionally, in 160 specimens, UHRF1 overexpression was significantly associated with LINE-1 hypomethylation (P=0.006) and poorer patient outcome (P=0.0023 in overall survival, and P=0.0469 in disease free survival).
Conclusion: UHRF1 overexpression was associated with LINE-1 hypomethylation and poorer patient outcome in ESCC. UHRF1 might be considered as a prognostic biomarker, and potential therapeutic target.

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臓器別:食道

手法別:トランスレーショナルリサーチ

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