Stool DNA testing is an emerging and attractive option for colorectal cancer (CRC) screening. We previously evaluated the feasibility of a stool DNA (sDNA) test of methylated SDC2 for CRC detection. The aim of this study was to assess its performance in a multicenter clinical trial setting. Each participant was required to undergo a sDNA test and a reference colonoscopy. The sDNA test consists of quantitative assessment of methylation status of SDC2 promoter. Results of real-time quantitative methylation-specific PCR were dichotomized as positive and negative, and the main evaluation indexes were sensitivity, specificity, and kappa value. All sDNA tests were performed and analyzed independently of colonoscopy. Among the 1110 participants from three clinical sites analyzed, 359 and 38 were diagnosed, respectively, with CRC and advanced adenomas by colonoscopy. The sensitivity of the sDNA test was 301/359 (83.8%) for CRC, 16/38 (42.1%) for advanced adenomas, and 134/154 (87.0%) for early stage CRC (stage I–II). Detection rate did not vary significantly according to age, tumor location, differentiation, and TNM stage, except for gender. The follow-up testing of 40 postoperative patients with CRC returned negative results as their tumors had been surgically removed. The specificity of the sDNA test was 699/713 (98.0%), and unrelated cancers and diseases did not seem to interfere with the testing. The kappa value was 0.84, implying an excellent diagnostic consistency between the sDNA test and colonoscopy. Noninvasive sDNA test using methylated SDC2 as the exclusive biomarker is a clinically viable and accurate CRC detection method. Chi-CTR-TRC-1900026409, retrospectively registered on October 8, 2019; http://www.chictr.org.cn/edit.aspx?pid=43888&htm=4 .

中文翻译：

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用于结直肠癌检测的新型甲基化 SDC2 粪便 DNA 检测的稳健性能：一项多中心临床研究


粪便 DNA 检测是结直肠癌 (CRC) 筛查的一种新兴且有吸引力的选择。我们之前评估了甲基化 SDC2 粪便 DNA (sDNA) 检测用于 CRC 检测的可行性。本研究的目的是评估其在多中心临床试验环境中的表现。每个参与者都需要接受 sDNA 测试和参考结肠镜检查。 sDNA 测试包括对 SDC2 启动子甲基化状态的定量评估。实时定量甲基化特异性PCR结果分为阳性和阴性，主要评价指标为敏感性、特异性和κ值。所有 sDNA 测试均独立于结肠镜检查进行和分析。在分析的三个临床中心的 1110 名参与者中，通过结肠镜检查分别诊断出 359 名和 38 名患有结直肠癌和晚期腺瘤。 sDNA 检测的敏感性对于 CRC 为 301/359 (83.8%)，对于晚期腺瘤为 16/38 (42.1%)，对于早期 CRC（I-II 期）为 134/154 (87.0%)。除性别外，检出率不会因年龄、肿瘤位置、分化程度和 TNM 分期而显着变化。 40 名 CRC 术后患者的后续检测结果呈阴性，因为他们的肿瘤已被手术切除。 sDNA测试的特异性为699/713（98.0%），不相关的癌症和疾病似乎不会干扰测试。 kappa 值为 0.84，这意味着 sDNA 测试和结肠镜检查之间具有极好的诊断一致性。使用甲基化SDC2作为唯一生物标志物的无创sDNA检测是一种临床上可行且准确的CRC检测方法。 Chi-CTR-TRC-1900026409，于2019年10月8日追溯注册； http://www.chictr.org.cn/edit.aspx?pid=43888&htm=4 。