Cysteine dioxygenase type 1

Progression of colorectal cancer (CRC) has been explained by genomic abnormalities along with the adenoma-carcinoma sequence theory (ACS). The aim of our study is to elucidate whether the promoter DNA methylation of the cancer-specific methylation gene, cysteine dioxygenase 1 (CDO1), contributes to...

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Veröffentlicht in:PloS one 2018-05, Vol.13 (5), p.e0194785
Hauptverfasser: Kojima, Keita, Nakamura, Takatoshi, Ohbu, Makoto, Katoh, Hiroshi, Ooizumi, Yosuke, Igarashi, Kazuharu, Ishii, Satoru, Tanaka, Toshimichi, Yokoi, Keigo, Nishizawa, Nobuyuki, Yokota, Kazuko, Kosaka, Yoshimasa, Sato, Takeo, Watanabe, Masahiko, Yamashita, Keishi
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container_issue 5
container_start_page e0194785
container_title PloS one
container_volume 13
creator Kojima, Keita
Nakamura, Takatoshi
Ohbu, Makoto
Katoh, Hiroshi
Ooizumi, Yosuke
Igarashi, Kazuharu
Ishii, Satoru
Tanaka, Toshimichi
Yokoi, Keigo
Nishizawa, Nobuyuki
Yokota, Kazuko
Kosaka, Yoshimasa
Sato, Takeo
Watanabe, Masahiko
Yamashita, Keishi
description Progression of colorectal cancer (CRC) has been explained by genomic abnormalities along with the adenoma-carcinoma sequence theory (ACS). The aim of our study is to elucidate whether the promoter DNA methylation of the cancer-specific methylation gene, cysteine dioxygenase 1 (CDO1), contributes to the carcinogenic process in CRC. The study group comprised 107 patients with CRC who underwent surgical resection and 90 adenomas treated with endoscopic resection in the Kitasato University Hospital in 2000. We analyzed the extent of methylation in each tissue using quantitative TaqMan methylation-specific PCR for CDO1. The methylation level increased along with the ACS process (p < 0.0001), and statistically significant differences were found between normal-appearing mucosa (NAM) and low-grade adenoma (p < 0.0001), and between low-grade adenoma and high-grade adenoma (p = 0.01), but not between high-grade adenoma and cancer with no liver metastasis. Furthermore, primary CRC cancers with liver metastasis harbored significantly higher methylation of CDO1 than those without liver metastasis (p = 0.02). As a result, the area under the curve by CDO1 promoter methylation was 0.96, 0.80, and 0.67 to discriminate cancer from NAM, low-grade adenoma from NAM, and low-grade adenoma from high-grade adenoma, respectively. CDO1 methylation accumulates during the ACS process, and consistently contributes to CRC progression.
doi_str_mv 10.1371/journal.pone.0194785
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subjects Colorectal cancer
Development and progression
DNA
Genetic aspects
Methylation
Promoters (Genetics)
title Cysteine dioxygenase type 1
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