Prediction of onset of remnant gastric cancer by promoter DNA methylation of CDO1/HOPX/Reprimo/E-cadherin

// Keita Kojima 1 , Naoko Minatani 1 , Hideki Ushiku 1 , Satoru Ishii 1 , Toshimichi Tanaka 1 , Keigo Yokoi 1 , Nobuyuki Nishizawa 1 , Yosuke Ooizumi 1 , Kazuharu Igarashi 1 , Kei Hosoda 1 , Hiromitsu Moriya 1 , Hiroaki Mieno 1 , Masahiko Watanabe 1 and Keishi Yamashita 1 , 2 1 Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0329, Japan 2 Division of Advanced Surgical Oncology, Research and Development Center for New Frontier, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0329, Japan Correspondence to: Keishi Yamashita, email: keishi23@med.kitasato-u.ac.jp Keywords: remnant gastric cancer; cysteine dioxygenase 1 (CDO1); homeodomain-only protein X (HOPX); Reprimo; E-cadherin Received: September 17, 2018 Accepted: January 19, 2019 Published: March 29, 2019 ABSTRACT Background: Early detection of remnant gastric cancer (RGC) is required to reduce the risk of death, but long-term endoscopic surveillance is difficult after gastrectomy. In this study, data for the methylation status of 4 methylation genes ( CDO1, HOPX, Reprimo, and E-cadherin ) to predict the onset of RGC are presented. Results: The 4 genes showed hypermethylation in RGC tumors in contrast to the corresponding non-cancerous mucosa tissues. The methylation level in the non-cancerous mucosa tissues of the initial surgery was obviously high in initial malignant disease for CDO1 ( P = 0.0001), while in initial benign one for E-cadherin ( P = 0.003). Promoter DNA methylation status in the remnant non-cancerous mucosa tissues together with the basic clinical data in turn predicted either initial malignant disease or initial benign disease with a high AUC score of 0.94, suggesting that methylation events are differentially recognized between the initial malignant and benign disease. We then finally confirmed that 4 genes hypermethylation of the non-cancerous tissues by biopsy prior to onset of RGC could predict terms until RGC occurred ( P < 0.0001). Methods: A total of 58 RGC patients were used to establish the model. The 4 genes promoter methylation were analyzed for DNA obtained from the patient’s specimens using quantitative methylation specific polymerase chain reaction. Conclusions: This risk model would help provide guidance for endoscopic surveillance plan of RGC after gastrectomy.