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

Autor: Hiroshi Katoh, Kazuko Yokota, Makoto Ohbu, Takeo Sato, Toshimichi Tanaka, Takatoshi Nakamura, Keita Kojima, Keigo Yokoi, Yosuke Ooizumi, Kazuharu Igarashi, Keishi Yamashita, Satoru Ishii, Yoshimasa Kosaka, Masahiko Watanabe, Nobuyuki Nishizawa
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Carcinogenesis
Colorectal cancer
lcsh:Medicine
Immunostaining
Biochemistry
Metastasis
0302 clinical medicine
Basic Cancer Research
Medicine and Health Sciences
Amino Acids
lcsh:Science
Promoter Regions
Genetic
Staining
DNA methylation
Multidisciplinary
Organic Compounds
Chemical Reactions
Methylation
Middle Aged
Prognosis
Adenomas
Chromatin
Nucleic acids
Chemistry
Oncology
030220 oncology & carcinogenesis
Physical Sciences
Epigenetics
Female
DNA modification
Colorectal Neoplasms
Chromatin modification
Research Article
Chromosome biology
Adenoma
Adult
Cell biology
Cysteine dioxygenase type 1
Adenocarcinoma
Research and Analysis Methods
03 medical and health sciences
Genetics
Biomarkers
Tumor
Carcinoma
medicine
Sulfur Containing Amino Acids
Humans
Cysteine
Aged
Colorectal Cancer
Biology and life sciences
business.industry
lcsh:R
Organic Chemistry
Chemical Compounds
Cysteine Dioxygenase
Cancers and Neoplasms
Proteins
Cancer
DNA
medicine.disease
digestive system diseases
030104 developmental biology
Specimen Preparation and Treatment
Cancer research
lcsh:Q
Gene expression
business
Zdroj: PLoS ONE
PLoS ONE, Vol 13, Iss 5, p e0194785 (2018)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0194785
Popis: 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.
Databáze: OpenAIRE
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