Abstract
Objective: To design a multi-targeted fecal DNA methylation kit and explore its value for clinical application among Chinese people. Methods: Based on previous research, a multi-targeted fecal DNA methylation detection kit, using four genes, was designed and clinically validated. Results: 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%. Conclusion: 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.