title: Hypermethylation of the MYOD1 gene is a novel prognostic factor in patients with colorectal cancer.
abstract: MYOD1 promoter methylation occurs in various malignancies including colorectal cancer. We analyzed MYOD1 methylation in 80 colorectal cancer and 74 adjacent normal tissues using MethyLight, which enabled quantitative DNA methylation analysis. The measured methylation value was expressed as a percentage of methylated reference (PMR). The results were compared with clinicopathological features and patient prognosis in order to investigate whether MYOD1 methylation may serve as an independent prognostic factor of colorectal cancer. MYOD1 promoter methylation was detectable in all samples and was significantly higher in tumor compared to normal mucosa, where the median level of methylation was 5.3 PMR (range 0.03-133.4) in normal mucosa and 42.3 PMR (range 0.44-742.9) in tumor. The methylation value of MYOD1 was higher with elder patients both in normal colonic mucosa (p=0.034) and in cancer tissues (p=0.0012). Patients without MYOD1 hypermethylation showed significantly longer survival than those with hypermethylation (p=0.0077). In multivariate analysis of prognostic factors, MYOD1 hypermethylation was a significant prognostic factor (p=0.015) independent to patients' age. These results suggest that MYOD1 hypermethylation plays an important role in colorectal cancer and may be a novel prognostic factor. In addition, quantitative methylation analysis by MethyLight is encouraged for other genes showing age-related and non-cancer-specific methylation.
authors.affiliation: Department of Surgery, Kanazawa University School of Medicine, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Hiranuma
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kawakami
authors.forename: Kaeko
authors.initials: K
authors.lastname: Oyama
authors.forename: Naohiro
authors.initials: N
authors.lastname: Ota
authors.forename: Kenji
authors.initials: K
authors.lastname: Omura
authors.forename: Go
authors.initials: G
authors.lastname: Watanabe
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017570:MyoD Protein / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D004273:DNA, Neoplasm; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein