Hideura Eizaburou, Suehiro Yutaka, Nishikawa Jun, Shuto Takuya, Fujimura Hiroyuki, Ito Shunsuke, Goto Atsushi, Hamabe Kouichi, Saeki Issei, Okamoto Takeshi, Higaki Shingo, Fujii Ikuei, Suzuki Chieko, Hoshida Tomomi, Matsumoto Toshihiko, Takami Taro, Sakaida Isao, Yamasaki Takahiro
Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
Cancers (Basel). 2020 Mar 26;12(4):789. doi: 10.3390/cancers12040789.
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.
胃癌筛查的主要方式局限于上消化道内镜检查和造影检查。前者具有侵入性，后者的假阴性率较高。因此，需要其他诊断策略。一种解决方案可能是液体活检。甲基化的RUNX3是一种著名的胃癌生物标志物，但当只有少量血清时，用传统的基于亚硫酸氢盐的甲基化检测方法很难检测到。我们开发了联合限制性数字PCR（CORD）检测方法，这是一种新的甲基化检测方法，无需对DNA进行亚硫酸氢盐处理，就能在少量DNA样本中对低至一个甲基化基因拷贝进行计数。我们使用50例早期胃癌患者和61例对照个体，通过CORD检测方法评估了甲基化RUNX3血清DNA检测对早期胃癌检测的敏感性和特异性。CORD检测方法对早期胃癌的敏感性为50.0%，特异性为80.3%。甲基化RUNX3拷贝与肿瘤大小、大量黏膜下浸润和淋巴血管浸润显著相关。治疗后，甲基化RUNX3拷贝的中位数显著下降。CORD检测方法可能为检测早期胃癌提供另一种筛查策略。
