Oncotarget

Research Papers:

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

PDF  |  Full Text  |  Supplementary Files  |  How to cite

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

Metrics: PDF 2023 views  |  Full Text 2897 views

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

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.