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Indoleamine 2, 3‐dioxygenase 1 promoter hypomethylation is associated with poor prognosis in patients with esophageal cancer
Indoleamine 2, 3‐dioxygenase 1 (IDO1) is a primary enzyme that generates immunosuppressive metabolites. It plays a major role in tumor immunology and is a potential immune‐based therapeutic target. We have reported that IDO1 protein expression was associated with an unfavorable clinical outcome in e...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549929/ https://www.ncbi.nlm.nih.gov/pubmed/31012515 http://dx.doi.org/10.1111/cas.14028 |
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author | Kiyozumi, Yuki Baba, Yoshifumi Okadome, Kazuo Yagi, Taisuke Ogata, Yoko Eto, Kojiro Hiyoshi, Yukiharu Ishimoto, Takatsugu Iwatsuki, Masaaki Iwagami, Shiro Miyamoto, Yuji Yoshida, Naoya Watanabe, Masayuki Baba, Hideo |
author_facet | Kiyozumi, Yuki Baba, Yoshifumi Okadome, Kazuo Yagi, Taisuke Ogata, Yoko Eto, Kojiro Hiyoshi, Yukiharu Ishimoto, Takatsugu Iwatsuki, Masaaki Iwagami, Shiro Miyamoto, Yuji Yoshida, Naoya Watanabe, Masayuki Baba, Hideo |
author_sort | Kiyozumi, Yuki |
collection | PubMed |
description | Indoleamine 2, 3‐dioxygenase 1 (IDO1) is a primary enzyme that generates immunosuppressive metabolites. It plays a major role in tumor immunology and is a potential immune‐based therapeutic target. We have reported that IDO1 protein expression was associated with an unfavorable clinical outcome in esophageal cancer. Recently, it has been reported that IDO1 expression is regulated by methylation of the IDO1 promoter. Thus, the aim of this study was to examine the relationship between IDO1 expression, IDO1 promoter methylation, and clinicopathological features in esophageal cancer. We first confirmed changes in IDO1 expression levels in vitro by treating cells with 5‐azacytidine. We then evaluated the relationship between IDO1 expression levels, IDO1 promoter methylation (bisulfite pyrosequencing), and clinicopathological features using 40 frozen samples and 242 formalin‐fixed, paraffin‐embedded samples resected from esophageal cancer patients. We treated cell lines with 5‐azacytidine, and the resulting hypomethylation induced significantly higher IDO1 expression (P < .001). In frozen samples, IDO1 expression levels correlated inversely with IDO1 promoter methylation levels (R = −0.47, P = .0019). Furthermore, patients in the IDO1 promoter hypomethylation group (n = 67) had a poor prognosis compared with those in the IDO1 promoter hypermethylation group (n = 175) (overall survival, P = .011). Our results showed that IDO1 promoter hypomethylation regulated IDO1 expression and was associated with a poor prognosis in esophageal cancer patients. |
format | Online Article Text |
id | pubmed-6549929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65499292019-06-07 Indoleamine 2, 3‐dioxygenase 1 promoter hypomethylation is associated with poor prognosis in patients with esophageal cancer Kiyozumi, Yuki Baba, Yoshifumi Okadome, Kazuo Yagi, Taisuke Ogata, Yoko Eto, Kojiro Hiyoshi, Yukiharu Ishimoto, Takatsugu Iwatsuki, Masaaki Iwagami, Shiro Miyamoto, Yuji Yoshida, Naoya Watanabe, Masayuki Baba, Hideo Cancer Sci Original Articles Indoleamine 2, 3‐dioxygenase 1 (IDO1) is a primary enzyme that generates immunosuppressive metabolites. It plays a major role in tumor immunology and is a potential immune‐based therapeutic target. We have reported that IDO1 protein expression was associated with an unfavorable clinical outcome in esophageal cancer. Recently, it has been reported that IDO1 expression is regulated by methylation of the IDO1 promoter. Thus, the aim of this study was to examine the relationship between IDO1 expression, IDO1 promoter methylation, and clinicopathological features in esophageal cancer. We first confirmed changes in IDO1 expression levels in vitro by treating cells with 5‐azacytidine. We then evaluated the relationship between IDO1 expression levels, IDO1 promoter methylation (bisulfite pyrosequencing), and clinicopathological features using 40 frozen samples and 242 formalin‐fixed, paraffin‐embedded samples resected from esophageal cancer patients. We treated cell lines with 5‐azacytidine, and the resulting hypomethylation induced significantly higher IDO1 expression (P < .001). In frozen samples, IDO1 expression levels correlated inversely with IDO1 promoter methylation levels (R = −0.47, P = .0019). Furthermore, patients in the IDO1 promoter hypomethylation group (n = 67) had a poor prognosis compared with those in the IDO1 promoter hypermethylation group (n = 175) (overall survival, P = .011). Our results showed that IDO1 promoter hypomethylation regulated IDO1 expression and was associated with a poor prognosis in esophageal cancer patients. John Wiley and Sons Inc. 2019-05-20 2019-06 /pmc/articles/PMC6549929/ /pubmed/31012515 http://dx.doi.org/10.1111/cas.14028 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Kiyozumi, Yuki Baba, Yoshifumi Okadome, Kazuo Yagi, Taisuke Ogata, Yoko Eto, Kojiro Hiyoshi, Yukiharu Ishimoto, Takatsugu Iwatsuki, Masaaki Iwagami, Shiro Miyamoto, Yuji Yoshida, Naoya Watanabe, Masayuki Baba, Hideo Indoleamine 2, 3‐dioxygenase 1 promoter hypomethylation is associated with poor prognosis in patients with esophageal cancer |
title | Indoleamine 2, 3‐dioxygenase 1 promoter hypomethylation is associated with poor prognosis in patients with esophageal cancer |
title_full | Indoleamine 2, 3‐dioxygenase 1 promoter hypomethylation is associated with poor prognosis in patients with esophageal cancer |
title_fullStr | Indoleamine 2, 3‐dioxygenase 1 promoter hypomethylation is associated with poor prognosis in patients with esophageal cancer |
title_full_unstemmed | Indoleamine 2, 3‐dioxygenase 1 promoter hypomethylation is associated with poor prognosis in patients with esophageal cancer |
title_short | Indoleamine 2, 3‐dioxygenase 1 promoter hypomethylation is associated with poor prognosis in patients with esophageal cancer |
title_sort | indoleamine 2, 3‐dioxygenase 1 promoter hypomethylation is associated with poor prognosis in patients with esophageal cancer |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549929/ https://www.ncbi.nlm.nih.gov/pubmed/31012515 http://dx.doi.org/10.1111/cas.14028 |
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