A novel plasma based early colorectal cancer screening assay base on methylated SDC2 and SFRP2

Background: Methylated SFRP2 was previously reported as a non-invasive biomarker for colorectal cancer (CRC) detection with a relatively low sensitivity for early stage CRC. The purpose of this study was to evaluate the performance of a new plasma based CRC screening assay, SpecColon test, which tested methylated SFRP2 and SDC2 simultaneously in a single qPCR reaction, in detecting CRC and advanced adenomas (AA). Method: One milliliter plasma of 122 CRC patients, 12 AA patients, 93 patients with benign polyps, and 91 normal individuals were collected from the Affiliated Hospital of Xuzhou Medical University, and all samples were examined by SpecColon test. Results: The sensitivities for detecting AA and CRC by methylated SFRP2 alone were 50.0% (95% CI: 22.2-77.7%) and 63.1% (95% CI: 53.9-71.5%) with a specificity of 90.1% (95% CI: 81.6-95.1%). The sensitivities by methylated SDC2 alone were 33.3% (95% CI: 11.3-64.6%) and 56.6% (95% CI: 47.3-65.4%) with a specificity of 95.6% (95% CI: 88.5-98.6%). However, when methylated SFRP2 and methylated SDC2 were combined, the sensitivities for AA and CRC detection improved to 58.3% (95% CI: 28.6-83.5%) and 76.2% (95% CI: 67.5-83.3%) with a specificity of 87.9% (95% CI: 79.0-93.5%). The positive detection rates of benign polyp group and normal control group showed no significant difference (p > 0.01), whereas AA and CRC groups had significantly higher positive detection rates than normal individual group (p < 0.001). Conclusion: The sensitivities for AA and early stage CRC by combined test of methylated SFRP2 and methylated SDC2, the so called SpecColon test, improved upon those by either biomarker alone without significant impact on the specificity. It has the potential to become a powerful, convenient and highly effective screening tool for early CRC screening.