Cysteine dioxygenase type 1 (CDO1) gene promoter methylation during the adenoma-carcinoma sequence in colorectal cancer.

Autor: Keita Kojima, Takatoshi Nakamura, Makoto Ohbu, Hiroshi Katoh, Yosuke Ooizumi, Kazuharu Igarashi, Satoru Ishii, Toshimichi Tanaka, Keigo Yokoi, Nobuyuki Nishizawa, Kazuko Yokota, Yoshimasa Kosaka, Takeo Sato, Masahiko Watanabe, Keishi Yamashita
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: PLoS ONE, Vol 13, Iss 5, p e0194785 (2018)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0194785
Popis: 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.
Databáze: Directory of Open Access Journals
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