Sensitive and specific detection of early gastric cancer with DNA methylation analysis of gastric washes.
Sensitive and specific detection of early gastric cancer with DNA methylation analysis of gastric washes.
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DOI：
10.1053/j.gastro.2009.02.085
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发表时间：
2009-06
期刊：
影响因子：
29.4
通讯作者：
Issa JP
中科院分区：
文献类型：
--
作者：
Watanabe Y;Kim HS;Castoro RJ;Chung W;Estecio MR;Kondo K;Guo Y;Ahmed SS;Toyota M;Itoh F;Suk KT;Cho MY;Shen L;Jelinek J;Issa JP
DNA甲基化异常是胃癌发生的早期和常见过程，可用于检测胃肿瘤。我们假设从胃洗涤液中回收的DNA的甲基化分析可用于检测胃癌。我们在7个胃癌细胞系和24个样本（训练集）中研究了51个候选基因，并确定了6个用于进一步研究。我们在一个由131例不同阶段的胃肿瘤组成的试验组中检测了这些基因的甲基化状态。最后，我们在40个原发性胃癌样本和113个非肿瘤性胃粘膜样本的不同人群中验证了6个候选基因。在训练集、测试集和验证集中，有6个基因（MINT25、RORA、GDNF、ADAM 23、PRDM5、MLF1）在胃癌和正常胃粘膜中出现频繁的差异甲基化。GDNF和MINT 25是早期胃癌最敏感的分子标志物，PRDM 5和MLF1是视野缺损的标志物。肿瘤活检和胃冲洗液中的甲基化水平之间存在密切相关性（r=0.5至0.9，p=0.03至0.001）。MINT25甲基化在胃液中的肿瘤检测方面具有最佳的灵敏度（90%）、特异性（96%）和ROC曲线下面积（0.961）。提示MINT 25是一种敏感、特异的胃癌筛查标志物。此外，我们还开发了一种通过胃洗液中DNA甲基化检测胃癌的新方法。
Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 non-neoplastic gastric mucosa samples. 6 genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer while PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r=0.5 to 0.9, p=0.03 to 0.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90%), specificity (96%), and area under the ROC curve (0.961) in terms of tumor detection in gastric washes. These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally we have developed a new methodology for gastric cancer detection by DNA methylation in gastric washes.
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影响因子：
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