Correlation between Stool DNA-based SDC2 Methylation Tests Combined with Tumor Markers with Pathological Features in Colorectal Cancer

Background: Colorectal cancer (CRC) screening is the most efficient strategy to reduce disease-related mortality. In this study, we aimed to investigate the association of a methylation-based stool DNA test with serum protein biomarker panel (CEA, CA125, CA199, and AFP) in CSC patients and their relationship with pathological features to improve the diagnostic efficacy and applicability in CSC in the Chinese population. Methods: In this double-blinded case-control study, we enrolled 150 participants from our hospital, including 50 CRC patients, 50 adenomas, and 50 healthy controls. We compared the cycling threshold (Ct) values of stool DNA-based SDC2 measured by quantitative methylation-specific PCR (MSP) in the three groups. We also evaluated the differences and correlation between serum concentrations of tumor biomarker and pathological features in patients with CSC, including TNM stage (I, II, III), tumor size, and lymph node metastasis. The discrimination performance of indexes was assessed using sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). Results: CSC was more common in middle-aged people and men. The methylation-based stool DNA test was not significantly correlated with other tumor indicators except CEA, and the difference was statistically significant. Compared with the normal control group, the combined diagnostic value of the methylation-based stool DNA test and tumor indicators was significantly higher than individual biomarkers alone, especially the methylation-based stool DNA test combined with CEA and AFP, which improved the AUC to 0.96. This combination can increase the positive rate of pathological stage diagnosis. Conclusions: Combining a methylation-based stool DNA test with CEA and AFP can significantly improve the diagnostic value of CRC and can be used to confirm the diagnosis of colorectal cancer. This combination can also be used as a reliable indicator identifying early-stage CRC patients and pathology. A large-scale study is underway to further define the clinical application of this method for the diagnosis of CRC among Chinese populations.