title: Promoter DNA methylation of CDO1 gene and its clinical significance in esophageal squamous cell carcinoma.
abstract: We have demonstrated that CDO1 methylation is frequently found in various cancers, including esophageal squamous cell carcinoma (ESCC), but its clinical relevance has remained elusive. CDO1 methylation was investigated in 169 ESCC patients who underwent esophagectomy between 1996 and 2007. CDO1 methylation was assessed by Q-MSP (quantitative methylation specific PCR), and its clinical significance, including its relationship to prognosis, was analyzed. (i) The median TaqMeth value of CDO1 methylation was 9.4, ranging from 0 to 279.5. CDO1 methylation was significantly different between cStage I and cStage II/III (P = 0.02). (ii) On the log-rank plot, the optimal cut-off value was determined to be 8.9; ESCC patients with high CDO1 methylation showed a significantly worse prognosis than those with low CDO1 methylation (P = 0.02). (iii) A multivariate Cox proportional hazards model identified only CDO1 hypermethylation as an independent prognostic factor (HR 2.00, CI 1.09-3.78, P = 0.03). (iv) CDO1 hypermethylation stratified ESCC patients' prognosis in cStage II/III for both neoadjuvant chemo(radio)therapy (NAC)-positive and NAC-negative cases. Moreover, the CDO1 methylation level was significantly lower in cases with Grade 2/3 than in those with Grade 0/1 (P = 0.02) among cStage II/III ESCC patients with NAC. Promoter DNA hypermethylation of CDO1 could be an independent prognostic factor in ESCC; it may also reflect NAC eradication of tumor cells in the primary tumors.
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ushiku
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katoh
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ema
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Minatani
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kojo
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Yokoi
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nishizawa
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Hosoda
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Moriya
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mieno
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Natsuya
authors.initials: N
authors.lastname: Katada
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Kikuchi
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D059186:Chemoradiotherapy, Adjuvant; D050558:Cysteine Dioxygenase / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000077277:Esophageal Squamous Cell Carcinoma; D016629:Esophagectomy; D004947:Esophagus / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: C579734:CDO1 protein, human; D050558:Cysteine Dioxygenase
keywords: Cysteine dioxygenase type 1 (CDO1); DNA methylation; esophageal squamous cell carcinoma; grade; prognosis