Identification of gastric cancer risk markers that are informative in individuals with past H. pylori infection
Identification of gastric cancer risk markers that are informative in individuals with past H. pylori infection
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DOI：
10.1007/s10120-011-0126-1
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发表时间：
2012-10-01
期刊：
影响因子：
7.4
通讯作者：
Ushijima, Toshikazu
中科院分区：
文献类型：
--
作者：
Nanjo, Sohachi;Asada, Kiyoshi;Ushijima, Toshikazu
幽门螺杆菌感染引起的表观基因组损伤在胃粘膜中积累，并在恶性肿瘤发生之前就已存在。在没有电流H的个体中。幽门螺杆菌感染后，特定CpG岛（CGI）的DNA甲基化水平与胃癌风险相关。由于对既往感染个体的风险评估在临床上很重要，我们在此旨在确定反映H.从55名胃癌患者（GC-Pt）（21名当前感染，34名过去感染）和55名健康志愿者（HV）（7名从未感染，21名当前感染，27名过去感染）获得胃粘膜。采用甲基化DNA免疫沉淀-CGI芯片检测高甲基化CGIs，甲基化特异性聚合酶链反应（PCR）检测其甲基化水平，并对3例既往感染的GC-Pt样本和1例既往感染的HV样本进行芯片分析，从中分离出15例高甲基化CGIs。其中7例既往感染的GC-Pt（n = 10）甲基化水平显著高于既往感染的HV（n = 10）（P < 0.001）。在验证队列中（21例GC-Pt既往感染，14例HV既往感染），7种新标记物在受试者工作特征曲线下的面积较大（0.78-0.84）和高比值比（12.7-36.0）与两个当前可用的标记相比（0.60-0.65，5.0-5.7）。我们确定了7个新的胃癌风险标志物，这些标志物在既往感染的个体中具有高度的信息性。
Epigenomic damage induced by Helicobacter pylori infection is accumulated in gastric mucosae before the development of malignancy. In individuals without current H. pylori infection, DNA methylation levels of specific CpG islands (CGIs) are associated with gastric cancer risk. Because risk estimation in individuals with past infection is clinically important, we here aimed to identify the risk markers that reflect epigenomic damage induced by H. pylori infection, and that are informative in these individuals.Gastric mucosae were obtained from 55 gastric cancer patients (GC-Pt) (21 with current infection and 34 with past infection) and 55 healthy volunteers (HV) (7 never-infected, 21 with current infection, and 27 with past infection). Hypermethylated CGIs were searched for by methylated DNA immunoprecipitation-CGI microarray, and methylation levels were analyzed by quantitative methylation-specific polymerase chain reaction (PCR).By microarray analysis of a pool of three samples from GC-Pt with past infection and another pool of samples from HV with past infection, 15 hypermethylated CGIs in the former pool were isolated. Seven of them had significantly higher methylation levels in GC-Pt with past infection (n = 10) than in HV with past infection (n = 10) (P < 0.001). In a validation cohort (21 GC-Pt with past infection and 14 HV with past infection), the seven new markers had large areas under the receiver-operating characteristic curves (0.78-0.84) and high odds ratios (12.7-36.0) compared with two currently available markers (0.60-0.65, 5.0-5.7).We identified seven novel gastric cancer risk markers that are highly informative in individuals with past infection.