Jin Heiying, Wang Jun, Zhang Chunxia
Department of colorectal surgery, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, 23 Nanhu Road, Nanjing 210017, China.
J Cancer. 2021 Jan 15;12(6):1644-1650. doi: 10.7150/jca.47214. eCollection 2021.
To design a multi-targeted fecal DNA methylation kit and explore its value for clinical application among Chinese people. Based on previous research, a multi-targeted fecal DNA methylation detection kit, using four genes, was designed and clinically validated. The methylation PCR from 279 patients met the requirements for the detection criteria. When all four molecular markers were negative, the negative predictive value (NPV) for colorectal cancer was 100% and the NPV for colorectal polyps was 84.21%. When one molecular marker was positive, the sensitivity (Se) for colorectal cancer was 76.4%-90.3%, the specificity (Sp) was 68.3-93.4%, and the positive predictive value (PPV) for colorectal cancer was 54.5-85.5%, and the NPV was 87.0-95.0%. For colorectal polyps, the Se was 41.0-52.5%, Sp 69.5-91.5%, and the PPV for colorectal polyps was 41.0-70.3%, the NPV was 75.2-79.3%. When two molecular markers were positive, the Se for colorectal cancer was 52.6-73.7%, the Sp was 93.2-98.3%, the PPV for colorectal cancer was 84.6-96.2%, the NPV was 76.0-85.3%. For colorectal polyps, the Se was 25.9-40.7%, Sp was 93.2-98.3%, PPV for screening of colorectal polyps was 63.6-90.0%, and the NPV was 73.3-78.1%. When three molecular markers were positive, the Se for colorectal cancer was 31.6-52.6%, the Sp was 98.3-100.0%, the PPV for colorectal cancer was 94.4-100.0%, the NPV was 73.4-76.6%. For colorectal polyps, the Se was 14.8-25.9%, and Sp was 98.3-100.0%, the PPV for colorectal polyps was 85.7-100.0%, the NPV was 72.0-74.7%. When four molecular markers were positive, the Se for colorectal cancer was 31.6%, the Sp was 100.0%, and the colorectal cancer PPV was 100.0% and the NPV was 69.4%. For polyps, the Se was 14.8%, Sp was 100.0%, and PPV was 100.0% and the NPV was 72.0%. The multi-targeted fecal DNA methylation detection kit for colorectal cancer and polyps had the sensitivity and specificity to meet the requirements for screening of colorectal tumors, which is easy to operate, has stable results and important clinical value. Among the four molecular markers studied, when one marker was positive for DNA methylation, colonoscopy was required; as the number of positive methylation markers increased, the specificity for the diagnosis gradually increased as well.
设计一种多靶点粪便DNA甲基化检测试剂盒，并探讨其在中国人群中的临床应用价值。基于先前的研究，设计了一种使用四个基因的多靶点粪便DNA甲基化检测试剂盒，并进行了临床验证。来自279例患者的甲基化PCR结果符合检测标准要求。当所有四个分子标志物均为阴性时，结直肠癌的阴性预测值（NPV）为100%，结直肠息肉的NPV为84.21%。当一个分子标志物为阳性时，结直肠癌的灵敏度（Se）为76.4%-90.3%，特异度（Sp）为68.3%-93.4%，结直肠癌的阳性预测值（PPV）为54.5%-85.5%，NPV为87.0%-95.0%。对于结直肠息肉，Se为41.0%-52.5%，Sp为69.5%-91.5%，结直肠息肉的PPV为41.0%-70.3%，NPV为75.2%-79.3%。当两个分子标志物为阳性时，结直肠癌的Se为52.6%-73.7%，Sp为93.2%-98.3%，结直肠癌的PPV为84.6%-96.2%，NPV为76.0%-85.3%。对于结直肠息肉，Se为25.9%-40.7%，Sp为93.2%-98.3%，筛查结直肠息肉的PPV为63.6%-90.0%，NPV为73.3%-78.1%。当三个分子标志物为阳性时，结直肠癌的Se为31.6%-52.6%，Sp为98.3%-100.0%，结直肠癌的PPV为94.4%-100.0%，NPV为73.4%-76.6%。对于结直肠息肉，Se为14.8%-25.9%，Sp为98.3%-100.0%，结直肠息肉的PPV为85.7%-100.0%，NPV为72.0%-74.7%。当四个分子标志物为阳性时，结直肠癌的Se为31.6%，Sp为100.0%，结直肠癌的PPV为100.0%，NPV为69.4%。对于息肉，Se为14.8%，Sp为100.0%，PPV为100.0%，NPV为72.0%。用于结直肠癌和息肉的多靶点粪便DNA甲基化检测试剂盒具有满足结直肠肿瘤筛查要求的灵敏度和特异度，操作简便，结果稳定，具有重要的临床价值。在所研究的四个分子标志物中，当一个标志物DNA甲基化为阳性时，需要进行结肠镜检查；随着甲基化阳性标志物数量的增加，诊断的特异度也逐渐增加。
