Evaluating the clinical performance of a novel dual-target stool DNA test for colorectal cancer detection

BACKGROUND AND AIMSMethylation-based stool DNA test showed a promising application for colorectal cancer (CRC) detection. This study aimed to evaluate the performance of a novel dual-target stool DNA test (DT-sDNA), composed of SDC2 and TFPI2, for the detection of CRC in clinical practice by using large-scale data from a multicenter clinical trial. METHODSWe enrolled 1,164 participants from three independent hospitals, including 320 CRC patients, 148 adenomas, 396 interfering diseases and 300 healthy controls. Their stool samples were collected and tested paralleled by DT-sDNA test under the guidance of standard operating procedure. All participants were dichotomized as positive and negative according to the cycling threshold (Ct) values measured by quantitative methylation-specific PCR (MSP). The diagnostic performance of DT-sDNA test was assessed by calculating indexes of sensitivity, specificity, and overall coincidence rate. Sanger sequencing and retesting of resected participants were performed to verify the accuracy and effectiveness of the test. RESULTSOverall, the sensitivity, specificity, and total coincidence rate of DT-sDNA test for CRC detection were 95.31%, 88.39%, and 90.29%, respectively, with the kappa value of 0.775 (P < 0.05) when comparing to non-CRCs. The sensitivities for the detection of advanced adenomas (n=38) and non-advanced adenomas (n=110) were 63.16% and 33.64%, and the specificity was 96.67% for healthy normal controls. The methylation status of SDC2 and TFPI2 in 375 samples were verified by Sanger sequencing and the average coincidence rate reached 99.62%. The coincidence rate was 94.12% (n=32) for 34 participants that undertook DT-sDNA test again after surgical resection. These results demonstrated high accuracy of the DT-sDNA test in discriminating CRCs from other diseases and healthy controls. CONCLUSIONSThe novel DT-sDNA test showed good performance for the diagnosis of colorectal cancer in clinical practice; fda.hubei.gov.cn number; 20190020787.