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01-02-2019 | Translational Research and Biomarkers

Epigenetic Status of CDO1 Gene May Reflect Chemosensitivity in Colon Cancer with Postoperative Adjuvant Chemotherapy

Authors: Keigo Yokoi, MD, PhD, Hiroki Harada, MD, Kazuko Yokota, MD, Satoru Ishii, MD, PhD, Toshimichi Tanaka, MD, PhD, Nobuyuki Nishizawa, MD, PhD, Masashi Shimazu, MD, Ken Kojo, MD, PhD, Hirohisa Miura, MD, Takahiro Yamanashi, MD, PhD, Takeo Sato, MD, PhD, Takatoshi Nakamura, MD, PhD, Masahiko Watanabe, MD, PhD, FACS, Keishi Yamashita, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Issue 2/2019

Abstract

Background

Cysteine dioxygenase type 1 (CDO1) acts as a tumor suppressor gene, and its expression is regulated by promoter DNA methylation in human cancer. The metabolic product mediated by CDO1 enzyme increases mitochondrial membrane potential (MMP), putatively representing chemoresistance. The aim of this study is to investigate the functional relevance of CDO1 gene in colon cancer with chemotherapy.

Patients and Methods

We investigated 170 stage III colon cancer patients for CDO1 methylation by using quantitative methylation-specific polymerase chain reaction (PCR). To elucidate the functional role of CDO1 gene in colorectal cancer (CRC) biology, we established cell lines that stably express CDO1 gene and evaluated chemosensitivity, MMP, and tolerability assay including anaerobic environment.

Results

Hypermethylation of CDO1 gene was an independent prognostic factor for stage III colon cancer on multivariate prognostic analysis. Surprisingly, patients with CDO1 hypermethylation exhibited better prognosis than those with CDO1 hypomethylation in stage III colon cancer with postoperative chemotherapy (P = 0.03); however, a similar finding was not seen in those without postoperative chemotherapy. In some CRC cell lines, forced expression of CDO1 gene increased MMP accompanied by chemoresistance and/or tolerance under hypoxia.

Conclusion

CDO1 methylation may be a useful biomarker to increase the number of stage III colon cancer patients who can be saved by adjuvant therapy. Such clinical relevance may represent the functionally oncogenic property of CDO1 gene through MMP activity.

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Title: Epigenetic Status of CDO1 Gene May Reflect Chemosensitivity in Colon Cancer with Postoperative Adjuvant Chemotherapy
Authors: Keigo Yokoi, MD, PhD
Hiroki Harada, MD
Kazuko Yokota, MD
Satoru Ishii, MD, PhD
Toshimichi Tanaka, MD, PhD
Nobuyuki Nishizawa, MD, PhD
Masashi Shimazu, MD
Ken Kojo, MD, PhD
Hirohisa Miura, MD
Takahiro Yamanashi, MD, PhD
Takeo Sato, MD, PhD
Takatoshi Nakamura, MD, PhD
Masahiko Watanabe, MD, PhD, FACS
Keishi Yamashita, MD, PhD, FACS
Publication date: 01-02-2019
Publisher: Springer International Publishing
Published in: Annals of Surgical Oncology / Issue 2/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-018-6865-z

At a glance: The STEP trials

Springer Medicine

Epigenetic Status of CDO1 Gene May Reflect Chemosensitivity in Colon Cancer with Postoperative Adjuvant Chemotherapy

Abstract

Background

Patients and Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Patients and Methods

Results

Conclusion

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