Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
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Predictive Significance of Promoter DNA Methylation of Cysteine Dioxygenase Type 1 (CDO1) in Metachronous Gastric Cancer

  • Kubota, Yo (Department of Gastroenterology, Kitasato University School of Medicine) ;
  • Tanabe, Satoshi (Division of Therapeutic Endoscopy, Department of Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine) ;
  • Azuma, Mizutomo (Department of Gastroenterology, Kitasato University School of Medicine) ;
  • Horio, Kazue (Department of Gastroenterology, Kitasato University School of Medicine) ;
  • Fujiyama, Yoshiki (Division of Advanced Surgical Oncology, Department of Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine) ;
  • Soeno, Takafumi (Division of Advanced Surgical Oncology, Department of Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine) ;
  • Furue, Yasuaki (Department of Gastroenterology, Kitasato University School of Medicine) ;
  • Wada, Takuya (Department of Gastroenterology, Kitasato University School of Medicine) ;
  • Watanabe, Akinori (Department of Gastroenterology, Kitasato University School of Medicine) ;
  • Ishido, Kenji (Department of Gastroenterology, Kitasato University School of Medicine) ;
  • Katada, Chikatoshi (Department of Gastroenterology, Kitasato University School of Medicine) ;
  • Yamashita, Keishi (Division of Advanced Surgical Oncology, Department of Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine) ;
  • Koizumi, Wasaburo (Department of Gastroenterology, Kitasato University School of Medicine) ;
  • Kusano, Chika (Department of Gastroenterology, Kitasato University School of Medicine)
  • Received : 2021.08.30
  • Accepted : 2021.11.15
  • Published : 2021.12.31
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Abstract

Purpose: Promoter DNA methylation of various genes has been associated with metachronous gastric cancer (MGC). The cancer-specific methylation gene, cysteine dioxygenase type 1 (CDO1), has been implicated in the occurrence of residual gastric cancer. We evaluated whether DNA methylation of CDO1 could be a predictive biomarker of MGC using specimens of MGC developing on scars after endoscopic submucosal dissection (ESD). Materials and Methods: CDO1 methylation values (TaqMeth values) were compared between 33 patients with early gastric cancer (EGC) with no confirmed metachronous lesions at >3 years after ESD (non-MGC: nMGC group) and 11 patients with MGC developing on scars after ESD (MGCSE groups: EGC at the first ESD [MGCSE-1 group], EGC at the second ESD for treating MGC developing on scars after ESD [MGCSE-2 group]). Each EGC specimen was measured at five locations (at tumor [T] and the 4-point tumor-adjacent noncancerous mucosa [TAM]). Results: In the nMGC group, the TaqMeth values for T were significantly higher than that for TAM (P=0.0006). In the MGCSE groups, TAM (MGCSE-1) exhibited significantly higher TaqMeth values than TAM (nMGC) (P<0.0001) and TAM (MGCSE-2) (P=0.0041), suggesting that TAM (MGCSE-1) exhibited CDO1 hypermethylation similar to T (P=0.3638). The area under the curve for discriminating the highest TaqMeth value of TAM (MGCSE-1) from that of TAM (nMGC) was 0.81, and using the cut-off value of 43.4, CDO1 hypermethylation effectively enriched the MGCSE groups (P<0.0001). Conclusions: CDO1 hypermethylation has been implicated in the occurrence of MGC, suggesting its potential as a promising MGC predictor.

Keywords

Acknowledgement

The authors would like to thank the Parents' Association Grant of Kitasato University, School of Medicine for funding this study, and Editage, Cactus Communications, Tokyo, Japan, for proofreading the manuscript.

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