Kojima Keita, Minatani Naoko, Ushiku Hideki, Ishii Satoru, Tanaka Toshimichi, Yokoi Keigo, Nishizawa Nobuyuki, Ooizumi Yosuke, Igarashi Kazuharu, Hosoda Kei, Moriya Hiromitsu, Mieno Hiroaki, Watanabe Masahiko, Yamashita Keishi
Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0329, Japan.
Division of Advanced Surgical Oncology, Research and Development Center for New Frontier, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0329, Japan.
Oncotarget. 2019 Mar 29;10(25):2423-2434. doi: 10.18632/oncotarget.26814.
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 ( and ) to predict the onset of RGC are presented.
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 ( = 0.0001), while in initial benign one for ( = 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 ( < 0.0001).
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.
This risk model would help provide guidance for endoscopic surveillance plan of RGC after gastrectomy.
为降低残胃癌（RGC）的死亡风险，需要早期检测，但胃切除术后长期的内镜监测存在困难。在本研究中，我们展示了4个甲基化基因（和）的甲基化状态数据，以预测RGC的发病情况。
与相应的非癌黏膜组织相比，这4个基因在RGC肿瘤中表现为高甲基化。对于（=0.0001），初次恶性疾病患者初次手术时非癌黏膜组织中的甲基化水平明显较高；而对于（=0.003），初次良性疾病患者中则较高。残余非癌黏膜组织中的启动子DNA甲基化状态与基本临床数据相结合，依次预测初次恶性疾病或初次良性疾病，AUC得分为0.94，表明甲基化事件在初次恶性疾病和良性疾病之间存在差异识别。然后我们最终证实，在RGC发病前通过活检检测非癌组织中4个基因的高甲基化可以预测RGC发生的时间（<0.0001）。
共纳入58例RGC患者建立模型。使用定量甲基化特异性聚合酶链反应分析从患者标本中获取的DNA的4个基因启动子甲基化情况。
该风险模型将有助于为胃切除术后RGC的内镜监测计划提供指导。
