Abstract
BACKGROUND: Colorectal cancer (CRC) screening can effectively reduce disease-related mortality by detecting CRC at earlier stages. We have previously demonstrated that the presence of SDC2 methylation in stool DNA is significantly associated with the occurrence of CRC regardless of clinical stage. The aim of this study was to evaluate the clinical performance of stool DNA-based SDC2 methylation test for CRC. METHODS: Aberrant SDC2 methylation in stool-derived DNA was measured by linear target enrichment (LTE)-quantitative methylation-specific real-time PCR (qMSP). Duplicate reactions of meSDC2 LTE-qMSP test were performed for stool samples obtained from CRC patients representing all stages (0-IV) and asymptomatic individuals who were subsequently underwent colonoscopy examination. To determine the diagnostic value of test in CRC and control groups, sensitivity and specificity were evaluated by receiver operating characteristic curve analysis. RESULTS: Of 585 subjects who could be evaluated, 245 had CRC, 44 had various sizes of adenomatous polyps, and 245 had negative colonoscopy results. Stool DNA-based meSDC2 LTE-qMSP showed an overall sensitivity of 90.2% with AUC of 0.902 in detecting CRC (0-IV) not associated with tumor stage, location, sex, or age (P > 0.05), with a specificity of 90.2%. Sensitivity for detecting early stages (0-II) was 89.1% (114/128). This test also detected 66.7% (2/3) and 24.4% (10/41) of advanced and non-advanced adenomas, respectively. CONCLUSIONS: Results of this study validated the capability of stool DNA based-SDC2 methylation test by LTE-qMSP for early detection of CRC patient with high specificity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03146520 , Registered 10 May 2017, Retrospectively registered; however, control arm was prospectively registered.