Research Papers:

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

Keita Kojima, Naoko Minatani, Hideki Ushiku, Satoru Ishii, Toshimichi Tanaka, Keigo Yokoi, Nobuyuki Nishizawa, Yosuke Ooizumi, Kazuharu Igarashi, Kei Hosoda, Hiromitsu Moriya, Hiroaki Mieno, Masahiko Watanabe and Keishi Yamashita _

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Oncotarget. 2019; 10:2423-2434. https://doi.org/10.18632/oncotarget.26814

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Keita Kojima1, Naoko Minatani1, Hideki Ushiku1, Satoru Ishii1, Toshimichi Tanaka1, Keigo Yokoi1, Nobuyuki Nishizawa1, Yosuke Ooizumi1, Kazuharu Igarashi1, Kei Hosoda1, Hiromitsu Moriya1, Hiroaki Mieno1, Masahiko Watanabe1 and Keishi Yamashita1,2

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: [email protected]

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


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.

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