title: DNA diagnosis of peritoneal fluid cytology test by CDO1 promoter DNA hypermethylation in gastric cancer.
abstract: BACKGROUND
  Minimal residual disease of the peritoneum is challenging for early cancer detection in gastric cancer (GC). Utility of PCR amplification of cancer-derived DNA has been considered feasible due to its molecular stability, however such markers have never been available in GC clinics. We recently discovered cancer-specific methylation of CDO1 gene in GC, and investigated the clinical potential to detect the minimal residual disease.
  
  
  METHODS
  One hundred and two GC patients were investigated for peritoneal fluid cytology test (CY), and detection level of the promoter DNA methylation of CDO1 gene was assessed by quantitative methylation specific PCR (Q-MSP) in the sediments (DNA CY).
  
  
  RESULTS
  (1) CY1 was pathologically confirmed in 8 cases, while DNA CY1 was detected in 18 cases. All 8 CY1 were DNA CY1. (2) DNA CY1 was recognized in 14.3, 25.0, 20.0, and 42.9%, in macroscopic Type II, small type III, large type III, and type IV, respectively, while it was not recognized in Type 0/I/V. (3) DNA CY1 was prognostic relevance in gastric cancer (p = 0.0004), and its significance was robust among Type III/IV gastric cancer (p = 0.006 for overall survival and p = 0.0006 for peritoneal recurrence free survival). (4) The peritoneal recurrence was hardly seen in GC patients with potent perioperative chemotherapy among those with DNA CY1.
  
  
  CONCLUSIONS
  DNA CY1 detected by Q-MSP for CDO1 gene promoter DNA methylation has a great potential to detect minimal residual disease of the peritoneum in GC clinics as a novel DNA marker.
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ushiku
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ema
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Minatani
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kojo
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Yokoi
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nishizawa
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Hosoda
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Moriya
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mieno
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Natsuya
authors.initials: N
authors.lastname: Katada
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Kikuchi
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katoh
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan. gekaw@med.kitasato-u.ac.jp.
authors.forename: Masahiko
authors.identifier: http://orcid.org/0000-0002-9902-7371
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000368:Aged; D001202:Ascitic Fluid / Q000166:cytology; D050558:Cysteine Dioxygenase / Q000235:genetics*; D003581:Cytodiagnosis / Q000379:methods*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
chemical_list: C579734:CDO1 protein, human; D050558:Cysteine Dioxygenase
keywords: Cysteine dioxygenase type 1 (CDO1); DNA diagnosis; DNA methylation; Gastric cancer; Peritoneal fluid cytology test