Methylated and in stool specimens for Colorectal Cancer early detection: A cost-effective strategy for Chinese population.

The aim of this study was to evaluate the feasibility of combination of methylated and methylated (SpecColon test) in stool specimens for colorectal cancer (CRC) early detection and to optimize the cut-off value of methylated and methylated . Approximately 5 g of stool specimen each was collected from 420 subjects (291 in the training cohort and 129 in the validation cohort). Stool DNA was extracted and bisulfite-converted, followed by detection of methylated level of and . Youden index was employed to determine the cut-off value. The whole operating time for stool SpecColon test takes less than 5 hours. The limit of detection of combination of methylated and methylated was as low as 5 pg per reaction. The optimized cut-off value was methylated analyzed by 3/3 rule and methylated analyzed by 2/3 rule. In the training cohort, the sensitivities of stool SpecColon test for detecting AA and early stage CRC (stage 0-II) were 53.8% (95% CI: 26.1%-79.6%) and 89.1% (95% CI: 77.1%-95.5%) with a specificity of 93.5% (95% CI: 87.2%-96.9%), and the AUC for CRC diagnosis was 0.879 (95% CI: 0.830-0.928). Similar performance was achieved by SpecColon test also in the validation cohort, where its sensitivities for detecting AA and early stage CRC (stage 0-II) were 61.5% (95% CI: 32.3-84.9%) and 88.5% (95% CI: 68.5%-97.0%) with a specificity of 89.5% (95% CI: 74.3-96.7%). Combined detections of methylated and methylated in stool samples demonstrated high sensitivities and specificity for the detection of AA and early stage CRC. Therefore, this combination has the potential to become an accurate and cost-effective tool for CRC early detection.