Aberrant Methylation of FOXE1 Contributes to a Poor Prognosis for Patients with Colorectal Cancer.
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.
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.|Department of Surgery, Fukuoka City Hospital, Fukuoka, Japan.
Keishi
K
Sugimachi
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.|Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Tae
T
Matsumura
Department of Systems Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Teppei
T
Shimamura
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Hidenari
H
Hirata
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Ryutaro
R
Uchi
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Masami
M
Ueda
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Shotaro
S
Sakimura
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Tomohiro
T
Iguchi
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Hidetoshi
H
Eguchi
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Takaaki
T
Masuda
Department of Surgery, Fukuoka City Hospital, Fukuoka, Japan.
Kazutoyo
K
Morita
Department of Surgery, Fukuoka City Hospital, Fukuoka, Japan.
Kenji
K
Takenaka
Department of Surgery and Science, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
Yoshihiko
Y
Maehara
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Masaki
M
Mori
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan. kmimori@beppu.kyushu-u.ac.jp.
Koshi
K
Mimori
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012007:Rectum / Q000378:metabolism; D015996:Survival Rate
D014408:Biomarkers, Tumor; C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors