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

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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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.

Author information

Authors and Affiliations

  1. Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan

    Keishi Sugimachi, Tae Matsumura, Hidenari Hirata, Ryutaro Uchi, Masami Ueda, Shotaro Sakimura, Tomohiro Iguchi, Hidetoshi Eguchi, Takaaki Masuda & Koshi Mimori MD, PhD

  2. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

    Tae Matsumura & Masaki Mori

  3. Department of Systems Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Teppei Shimamura

  4. Department of Surgery and Science, Kyushu University Graduate School of Medicine, Fukuoka, Japan

    Yoshihiko Maehara

  5. Department of Surgery, Fukuoka City Hospital, Fukuoka, Japan

    Keishi Sugimachi, Kazutoyo Morita & Kenji Takenaka

Authors
  1. Keishi Sugimachi
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  2. Tae Matsumura
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  3. Teppei Shimamura
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  13. Yoshihiko Maehara
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  14. Masaki Mori
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  15. Koshi Mimori MD, PhD
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Corresponding author

Correspondence to Koshi Mimori MD, PhD.

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Sugimachi, K., Matsumura, T., Shimamura, T. et al. Aberrant Methylation of FOXE1 Contributes to a Poor Prognosis for Patients with Colorectal Cancer. Ann Surg Oncol 23, 3948–3955 (2016). https://doi.org/10.1245/s10434-016-5289-x

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  • DOI: https://doi.org/10.1245/s10434-016-5289-x

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