Aberrant methylation of microRNA-34b/c is a predictive marker of metachronous gastric cancer risk.
Aberrant methylation of microRNA-34b/c is a predictive marker of metachronous gastric cancer risk.
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DOI：
10.1007/s00535-013-0861-7
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发表时间：
2014-07
影响因子：
6.3
通讯作者：
Shinomura, Yasuhisa
中科院分区：
文献类型：
--
作者：
Suzuki, Ryo;Yamamoto, Eiichiro;Nojima, Masanori;Maruyama, Reo;Yamano, Hiro-o;Yoshikawa, Kenjiro;Kimura, Tomoaki;Harada, Taku;Ashida, Masami;Niinuma, Takeshi;Sato, Akiko;Nosho, Katsuhiko;Yamamoto, Hiroyuki;Kai, Masahiro;Sugai, Tamotsu;Imai, Kohzoh;Suzuki, Hiromu;Shinomura, Yasuhisa
异时性胃癌(GC)可在胃镜下切除后发展，不能根据临床特征进行预测。非癌性胃粘膜DNA甲基化异常与胃癌的发生密切相关，可能是胃癌风险的有用生物标记物。我们评估了DNA甲基化作为异时性胃癌风险生物标志物的临床应用价值。我们对129例胃癌根治性内窥镜切除术后的患者进行了定期随访。取胃窦和胃体非癌粘膜组织标本，用亚硫酸氢盐焦磷酸测序法进行miR-34b/c、SFRP1、SFRP2、SFRP5、DKK2和DKK3基因甲基化定量分析。使用Kaplan-Meier和Cox比例风险模型分析来评估甲基化对预测异时性胃癌发生风险的有效性。在随访期内，17例(13%)患者发生异时性GCs。胃体miR-34b/c、SFRP2和DKK2甲基化升高的患者异时性胃癌的累积发生率显著高于对照组。MiR-34b/c与异时性胃癌的风险相关性最强，高miR-34b/c甲基化组异时性胃癌的累积发生率明显高于低甲基化组。校正年龄、性别、幽门螺杆菌感染状况和病理结果的多因素分析显示，胃体miR-34b/c甲基化是异时性胃癌风险的独立预测因素。我们的结果提示，非癌胃体粘膜miR-34b/c的甲基化可能是预测异时性胃癌风险的有用生物标志物。本文的在线版本(doi：10.1007/s00535-0130861-7)包含补充材料，授权用户可以使用。
Metachronous gastric cancer (GC) can develop after endoscopic resection of GC and cannot be predicted based on clinical signature. Aberrant DNA methylation in noncancerous gastric mucosa is strongly implicated in gastric carcinogenesis and could be a useful biomarker of GC risk. We evaluated the clinical utility of DNA methylation as a biomarker of metachronous GC risk. We carried out scheduled follow-up endoscopy in 129 patients after curative endoscopic resection of GC. Biopsy specimens were collected from noncancerous mucosa in the gastric antrum and body, after which quantitative methylation analysis of miR-34b/c, SFRP1, SFRP2, SFRP5, DKK2 and DKK3 was carried out using bisulfite pyrosequencing. The utility of the methylation for predicting the risk of metachronous GC development was assessed using Kaplan–Meier and Cox proportional hazards model analyses. During the follow-up period, 17 patients (13 %) developed metachronous GCs. The cumulative incidence of metachronous GC was significantly higher among patients with elevated miR-34b/c, SFRP2 and DKK2 methylation in their gastric body. MiR-34b/c showed the strongest association with the risk of metachronous GC, and the cumulative incidence of metachronous GC was much higher in the high-miR-34b/c-methylation group than the low-methylation group. Multivariate analysis adjusted for age, sex, H. pylori status and pathological findings showed miR-34b/c methylation in gastric body to be an independent predictor of metachronous GC risk. Our results suggest that methylation of miR-34b/c in the mucosa of the noncancerous gastric body may be a useful biomarker for predicting the risk of metachronous GC. The online version of this article (doi:10.1007/s00535-013-0861-7) contains supplementary material, which is available to authorized users.
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影响因子：
8
作者：
Nojima, M.;Suzuki, H.;Shinomura, Y.
通讯作者：
Shinomura, Y.
影响因子：
29.4
作者：
Sepulveda, Antonia R.;Yao, Yuan;Graham, David Y.
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影响因子：
24.5
作者：
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影响因子：
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作者：
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通讯作者：
Ushijima, Toshikazu
影响因子：
6.3
作者：
Nakajima, Takeshi;Enomoto, Shotaro;Ushijima, Toshikazu
通讯作者：
Ushijima, Toshikazu