Combination of fecal SDC2 methylation with serum CEA/CA72–4 in screening of colorectal cancer and precancerous lesions

• A triple-marker strategy synergizes fecal DNA and serum tests for CRC screening. • This combination achieves near-complete (96.9%) sensitivity for colorectal cancer. • Half of precancerous advanced adenomas are identified by the combined approach. • The method surpasses standard blood tests in early detection capability. To explore the application value of fecal Syndecan-2 gene Methylation (mSDC2) detection, combined detection of serum Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 72–4 (CA72–4) in screening of Colorectal Cancer (CRC) and precancerous lesions. A total of 196 participants were enrolled in this case-control study from March to December 2023, including 65 with CRC, 38 with advanced adenomas, 33 with non-advanced adenomas, and 60 controls. The sensitivity, specificity, and Odds Ratios (OR) for serum CEA, CA72–4, and fecal mSDC2 were evaluated. The sensitivity of fecal mSDC2 for CRC was 86.2% (56/65), with a specificity of 96.7% (58/60), with an OR of 28.9 (95% CI 8.6–97.2, p < 0.001). The sensitivity in advanced adenomas was 34.2% (13/38). Serum CEA had a sensitivity of 56.9% (37/65) and a specificity of 96.7% (58/60) for CRC, with an OR of 5.7 (95% CI 2.0–16.4, p < 0.001). Combined detection of CEA and CA72–4 had a sensitivity of 69.2% (45/65) and a specificity of 81.6% (49/60). The triple combination (mSDC2 + CEA + CA72–4) achieved a sensitivity of 96.9% (63/65) and a specificity of 78.3% (47/60) in the CRC, and a sensitivity of 50% (19/38) for advanced adenomas. The combined detection had higher sensitivity than single detection, with statistically significant differences compared to serum-based detection (p < 0.001). Combining fecal mSDC2 with serum CEA and CA72–4 increased sensitivity for CRC detection in this single-center study, at the cost of reduced specificity. Validation in larger, screening-intended cohorts with predefined thresholds is warranted.