Combined Methylation Analysis of SDC2 and TFPI2 in Plasma: A Noninvasive Liquid Biopsy Approach for Early Detection of Colorectal Polyp

Early detection is crucial for improving survival rates in colorectal cancer (CRC). This study evaluates the non-invasive diagnosis of polyps by assessing the methylation status of the TFPI2 and SDC2 genes in plasma. This study enrolled 27 individuals with low-risk polyps (LRP), 27 with high-risk polyps (HRP), and 27 healthy controls. The quantitative methylation levels of TFPI2 and SDC2 genes were analyzed in plasma cell-free DNA (cfDNA) using the methylation-quantification endonuclease-resistant DNA (MethyQESD) method. Increased methylation percentages of both TFPI2 (TFPI2_1 and TFPI2_2) and SDC2 (SDC2_2) were observed in individuals with LRP and HRP. The combination of SDC2 and TFPI2 yielded an Area Under the Curve (AUC) of 0.732 (95% CI 0.78 to 0.96, p=0.001) with a sensitivity of 66% (95% CI 46% - 82%) and specificity of 77% (95 CI 56% - 91%) for LRP. For HRP, the AUC was 0.890 (95% CI 0.596 to 0.843, p<0.001) with a sensitivity of 70% (95% CI 51% - 84%) and specificity of 92% (95 CI 75% - 99%). The combined assessment of SDC2 and TFPI2 methylation presents a potential approach for the early non-invasive detection of CRC and its associated precancerous lesions.