Aberrant Methylation of FOXE1 Contributes to a Poor Prognosis for Patients with Colorectal Cancer

被引：11

作者：

Sugimachi, Keishi ^{[1
,5
]}

Matsumura, Tae ^{[1
,2
]}

Shimamura, Teppei ^{[3
]}

Hirata, Hidenari ^{[1
]}

Uchi, Ryutaro ^{[1
]}

Ueda, Masami ^{[1
]}

Sakimura, Shotaro ^{[1
]}

Iguchi, Tomohiro ^{[1
]}

Eguchi, Hidetoshi ^{[1
]}

Masuda, Takaaki ^{[1
]}

Morita, Kazutoyo ^{[5
]}

Takenaka, Kenji ^{[5
]}

Maehara, Yoshihiko ^{[4
]}

Mori, Masaki ^{[2
]}

Mimori, Koshi ^{[1
]}

机构：

[1] Kyushu Univ, Beppu Hosp, Dept Surg, Beppu, Oita, Japan

[2] Osaka Univ, Dept Surg Gastroenterol, Grad Sch Med, Osaka, Japan

[3] Nagoya Univ, Dept Syst Biol, Grad Sch Med, Nagoya, Aichi, Japan

[4] Kyushu Univ, Dept Surg & Sci, Grad Sch Med, Fukuoka, Japan

[5] Fukuoka City Hosp, Dept Surg, Fukuoka, Japan

来源：

ANNALS OF SURGICAL ONCOLOGY | 2016年 / 23卷 / 12期

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

DNA METHYLATION; HYPERMETHYLATION; DISCOVERY; GENES;

D O I：

10.1245/s10434-016-5289-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Hypermethylation of DNA silences gene expression and is an important event in colorectal cancer (CRC). This study aimed to identify aberrantly methylated genes that contribute to a poor prognosis for patients with CRC. The study comprehensively explored DNA methylation microarray profiles from 396 CRC samples and 45 normal control samples in a database and selected aberrantly methylated transcription factors associated with prognosis and metastasis. Using quantitative reverse transcription polymerase chain reaction, the identified genes in 140 patients with CRC were validated to assess the relationship between expression of methylated genes and prognosis. In the study, FOXE1 was newly identified as a gene associated with prognosis and metastasis in CRC. Expression of FOXE1 in CRC tissues was significantly lower than in normal colorectal tissues (p = 0.01). The survival rate for the patients with low expression of FOXE1 was significantly lower than that for patients with high expression of FOXE1 in uni- and multivariate analyses. Inhibition of DNA methylation recovered FOXE1 expression in CRC cells. Methylation-mediated silencing of FOXE1 expression was shown to be a potential prognostic factor in CRC.

引用

页码：3948 / 3955

页数：8