RRC ID 52704
著者 Kojima K, Nakamura T, Ohbu M, Katoh H, Ooizumi Y, Igarashi K, Ishii S, Tanaka T, Yokoi K, Nishizawa N, Yokota K, Kosaka Y, Sato T, Watanabe M, Yamashita K.
タイトル Cysteine dioxygenase type 1 (CDO1) gene promoter methylation during the adenoma-carcinoma sequence in colorectal cancer.
ジャーナル PLoS One
Abstract BACKGROUND: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.
METHODS: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.
RESULTS: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.
CONCLUSIONS:CDO1 methylation accumulates during the ACS process, and consistently contributes to CRC progression.
巻・号 13(5)
ページ e0194785
公開日 2018-5-10
DOI 10.1371/journal.pone.0194785
PII PONE-D-17-31030
PMID 29746493
PMC PMC5944981
MeSH Adenocarcinoma / diagnosis* Adenocarcinoma / enzymology Adenocarcinoma / genetics Adenoma / diagnosis* Adenoma / enzymology Adenoma / genetics Adult Aged Biomarkers, Tumor Colorectal Neoplasms / diagnosis* Colorectal Neoplasms / enzymology Colorectal Neoplasms / genetics Cysteine Dioxygenase / genetics* DNA Methylation* Female Humans Male Middle Aged Prognosis Promoter Regions, Genetic*
IF 2.74
引用数 13
リソース情報
ヒト・動物細胞 HCT116(RCB2979)