Gene methylation profile of gastric cancerous tissue according to tumor site in the stomach.
Gene methylation profile of gastric cancerous tissue according to tumor site in the stomach.
复制标题
DOI：
10.1186/s12885-016-2077-8
复制
发表时间：
2016-01-26
期刊：
影响因子：
3.8
通讯作者：
Juozaityte E
中科院分区：
文献类型：
--
作者：
Kupcinskaite-Noreikiene R;Ugenskiene R;Noreika A;Rudzianskas V;Gedminaite J;Skieceviciene J;Juozaityte E
关于胃癌发生过程中不同基因启动子区甲基化的研究已有相当多的资料。然而，缺乏关于这种表观遗传过程在起源于胃不同部位的肿瘤中如何不同的信息。本研究的目的是评估MLH 1，MGMT和DAPK-1基因在不同胃部位癌组织中的甲基化谱。样本采集自2009-2012年在立陶宛健康科学大学医院考纳斯诊所接受胃癌手术的81名胃腺癌患者。甲基化特异性PCR检测基因甲基化。该研究得到了立陶宛生物医学研究伦理委员会的批准。在胃上、中、下三分之一的癌组织中，MLH 1的甲基化频率分别为11.1%、23.1%和45.4%; MGMT的甲基化频率分别为22.2%、30.8%和57.6%; DAPK-1的甲基化频率分别为44.4%、48.7%和51.5%。MLH 1和MGMT甲基化在胃的下三分之一比在上三分之一更常见（p < 0.05）。在中间三分之一，DAPK-1启动子甲基化与淋巴结中更晚期的疾病（N2-3与N 0 -1 [p = 0.02]）和晚期肿瘤分期（III期而不是I-II期[p = 0.05]）相关。当肿瘤位于胃的下三分之一时，MLH 1和MGMT甲基化呈负相关（系数，-0.48; p = 0.01）。DAPK-1和MLH 1甲基化在胃中三分之一的肿瘤中呈负相关（系数，-0.41; p = 0.01）。基因启动子甲基化取决于胃癌的位置。
There is considerable information on the methylation of the promoter regions of different genes involved in gastric carcinogenesis. However, there is a lack of information on how this epigenetic process differs in tumors originating at different sites in the stomach. The aim of this study is to assess the methylation profiles of the MLH1, MGMT, and DAPK-1 genes in cancerous tissues from different stomach sites. Samples were acquired from 81 patients suffering stomach adenocarcinoma who underwent surgery for gastric cancer in the Lithuanian University of Health Sciences Hospital Kaunas Clinics in 2009–2012. Gene methylation was investigated with methylation-specific PCR. The study was approved by the Lithuanian Biomedical Research Ethics Committee. The frequencies of methylation in cancerous tissues from the upper, middle, and lower thirds of the stomach were 11.1, 23.1, and 45.4 %, respectively, for MLH1; 22.2, 30.8, and 57.6 %, respectively, for MGMT; and 44.4, 48.7, and 51.5 %, respectively, for DAPK-1. MLH1 and MGMT methylation was observed more often in the lower third of the stomach than in the upper third (p < 0.05). In the middle third, DAPK-1 promoter methylation was related to more-advanced disease in the lymph nodes (N2–3 compared with N0–1 [p = 0.02]) and advanced tumor stage (stage III rather than stages I–II [p = 0.05]). MLH1 and MGMT methylation correlated inversely when the tumor was located in the lower third of the stomach (coefficient, –0.48; p = 0.01). DAPK-1 and MLH1 methylation correlated inversely in tumors in the middle-third of the stomach (coefficient, –0.41; p = 0.01). Gene promoter methylation depends on the gastric tumor location.