Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer
Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer
复制标题
循环血中游离甲基化RUNX3基因DNA检测对早期胃癌诊断具有重要价值
DOI：
10.3390/cancers12040789
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发表时间：
2020-04-01
期刊：
影响因子：
5.2
通讯作者：
Yamasaki, Takahiro
中科院分区：
文献类型：
--
作者：
Hideura, Eizaburou;Suehiro, Yutaka;Yamasaki, Takahiro
胃癌筛查的主要方式仅限于上消化道内窥镜检查和造影。前者是侵入性的，后者具有高假阴性率。因此，需要替代诊断策略。一种解决方案可以是液体活检。甲基化的RUNX3是胃癌的一种众所周知的生物标志物，但当只有少量血清可用时，用传统的基于亚硫酸氢盐的甲基化测定法很难检测到。我们开发了联合限制性数字PCR（CORD）测定，这是一种新的甲基化测定，允许在小样本DNA中计数少至一个甲基化基因拷贝，而无需DNA亚硫酸氢盐处理。我们使用50例早期胃癌患者和61例对照个体，评估了通过CORD检测法检测甲基化RUNX3血清DNA检测早期胃癌的灵敏度和特异性。CORD检测对早期胃癌的敏感性为50.0%，特异性为80.3%。甲基化RUNX3拷贝数与肿瘤大小、大量粘膜下浸润和淋巴管浸润显著相关。治疗后，甲基化RUNX3拷贝数的中位数显著降低。CORD检测可能提供一种替代的筛查策略，以检测甚至早期胃癌。
The main modalities for gastric cancer screening are limited to upper gastrointestinal endoscopy and contrast radiography. The former is invasive, and the latter has high false-negative rates. Thus, alternative diagnostic strategies are required. One solution may be a liquid biopsy. Methylated RUNX3 is a well-known biomarker of gastric cancer but it is very difficult to detect with conventional bisulfite-based methylation assays when only a small amount of serum is available. We developed the combined restriction digital PCR (CORD) assay, a new methylation assay allowing for the counting of as little as one copy of a methylated gene in a small sample of DNA without necessitating DNA bisulfite treatment. We evaluated the sensitivity and specificity of the serum DNA testing of methylated RUNX3 by the CORD assay for the detection of early gastric cancer using 50 patients with early gastric cancer and 61 control individuals. The CORD assay had a sensitivity of 50.0% and a specificity of 80.3% for early gastric cancer. Methylated RUNX3 copies were significantly associated with tumor size, massive submucosal invasion, and lymph-vascular invasion. After the treatment, the median number of methylated RUNX3 copies was significantly decreased. The CORD assay may provide an alternative screening strategy to detect even early-stage gastric cancer.