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Annals of Surgical Oncology

, Volume 23, Issue 12, pp 3948–3955 | Cite as

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

  • Keishi Sugimachi
  • Tae Matsumura
  • Teppei Shimamura
  • Hidenari Hirata
  • Ryutaro Uchi
  • Masami Ueda
  • Shotaro Sakimura
  • Tomohiro Iguchi
  • Hidetoshi Eguchi
  • Takaaki Masuda
  • Kazutoyo Morita
  • Kenji Takenaka
  • Yoshihiko Maehara
  • Masaki Mori
  • Koshi Mimori
Gastrointestinal Oncology

ABSTRACT

Background

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.

Methods

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.

Results

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.

Conclusions

Methylation-mediated silencing of FOXE1 expression was shown to be a potential prognostic factor in CRC.

Keywords

Adenoid Cystic Carcinoma Cutaneous Squamous Cell Carcinoma FOXE1 Gene FOXE1 Expression Infinium Human Methylation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank K. Oda, M. Kasagi, and T. Kawano for their technical assistance. This work was supported in part by the following grants and foundations: Japan Science and Technology Agency (JST), Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research (Grant Nos. 24592005, 25461953, 25861199, 25861200, and 26861085), Japan Science and Technology Agency (JSTA) (A-step grant no. AS242Z03987P), the Founding Program for Next Generation World-Leading Researchers (LS094), and the Daiwa Securities Health Foundation.

Conflict of interest

There are no conflicts of interest.

Supplementary material

10434_2016_5289_MOESM1_ESM.xlsx (9 kb)
Supplementary material 1 (XLSX 9 kb)
10434_2016_5289_MOESM2_ESM.xlsx (10 kb)
Supplementary material 2 (XLSX 10 kb)

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Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • Keishi Sugimachi
    • 1
    • 5
  • Tae Matsumura
    • 1
    • 2
  • Teppei Shimamura
    • 3
  • Hidenari Hirata
    • 1
  • Ryutaro Uchi
    • 1
  • Masami Ueda
    • 1
  • Shotaro Sakimura
    • 1
  • Tomohiro Iguchi
    • 1
  • Hidetoshi Eguchi
    • 1
  • Takaaki Masuda
    • 1
  • Kazutoyo Morita
    • 5
  • Kenji Takenaka
    • 5
  • Yoshihiko Maehara
    • 4
  • Masaki Mori
    • 2
  • Koshi Mimori
    • 1
  1. 1.Department of SurgeryKyushu University Beppu HospitalBeppuJapan
  2. 2.Department of Gastroenterological SurgeryOsaka University Graduate School of MedicineOsakaJapan
  3. 3.Department of Systems BiologyNagoya University Graduate School of MedicineNagoyaJapan
  4. 4.Department of Surgery and ScienceKyushu University Graduate School of MedicineFukuokaJapan
  5. 5.Department of SurgeryFukuoka City HospitalFukuokaJapan

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