Integrated fecal SDC2 methylation and serum tumor markers improve noninvasive detection of colorectal cancer
- 1Department of Laboratory Medicine, The First People’s Hospital of Jiangxia District, Wuhan City, Hubei University of Medicine
Abstract
Background: Fecal SDC2 methylation is a promising noninvasive biomarker for colorectal cancer (CRC), whereas serum tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA242, and CA50, are primarily used for postoperative surveillance and have limited value as standalone early diagnostic markers. This study evaluated the diagnostic performance of combining fecal SDC2 methylation with these four serum markers for CRC detection.
Methods: A total of 354 participants were enrolled, including 55 with CRC, 188 with adenoma/polyps, 106 with non-tumor/inflammatory conditions, and 5 with other undetermined lesions. Fecal SDC2 methylation was assessed by quantitative methylation-specific PCR, and serum markers were measured via electrochemiluminescence immunoassays. Diagnostic performance was evaluated using multivariable logistic regression and receiver operating characteristic (ROC) curve analysis. AUCs with 95% confidence intervals were calculated, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated at the Youden-optimal threshold.
Results: Fecal SDC2 methylation levels were significantly higher in CRC patients compared to those with adenomas or non-tumor lesions. Fecal SDC2 Ct value alone yielded an AUC of 0.814 (95% CI, 0.751-0.876). The AUC increased to 0.866 (95% CI, 0.814-0.918) after addition of CEA and to 0.872 (95% CI, 0.818-0.926) for the full model incorporating CEA, CA19-9, CA242, and CA50. At the Youden-optimal threshold, the full model achieved a sensitivity of 87.3% (95% CI, 76.0%-93.7%), specificity of 78.6% (95% CI, 73.6%-82.9%), PPV of 42.9% (95% CI, 34.1%-52.1%), and NPV of 97.1% (95% CI, 94.2%-98.6%). In contrast, individual serum markers showed limited diagnostic performance, with AUC values of 0.709 (CEA), 0.666 (CA19-9), 0.495 (CA242), and 0.567 (CA50).
Conclusion: Integration of fecal SDC2 Ct values with serum tumor markers showed a modest improvement in the noninvasive discrimination of CRC compared with SDC2 alone. Prospective external and stage-specific validation is required before clinical screening implementation.
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BibTeX
@article{tong2026integrated,
title = {{Integrated fecal SDC2 methylation and serum tumor markers improve noninvasive detection of colorectal cancer}},
author = {Shenglan Tong and Kang Rao and Man Sun and Yang Wu and Yan Dong and Changgang Xiang},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1919347},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1919347/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrated fecal SDC2 methylation and serum tumor markers improve noninvasive detection of colorectal cancer
AU - Shenglan Tong
AU - Kang Rao
AU - Man Sun
AU - Yang Wu
AU - Yan Dong
AU - Changgang Xiang
PY - 2026
DA - 2026/10/21
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1919347
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1919347/full
AB - Background: Fecal SDC2 methylation is a promising noninvasive biomarker for colorectal cancer (CRC), whereas serum tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA242, and CA50, are primarily used for postoperative surveillance and have limited value as standalone early diagnostic markers. This study evaluated the diagnostic performance of combining fecal SDC2 methylation with these four serum markers for CRC detection. Methods: A total of 354 participants were enrolled, including 55 with CRC, 188 with adenoma/polyps, 106 with non-tumor/inflammatory conditions, and 5 with other undetermined lesions. Fecal SDC2 methylation was assessed by quantitative methylation-specific PCR, and serum markers were measured via electrochemiluminescence immunoassays. Diagnostic performance was evaluated using multivariable logistic regression and receiver operating characteristic (ROC) curve analysis. AUCs with 95% confidence intervals were calculated, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated at the Youden-optimal threshold. Results: Fecal SDC2 methylation levels were significantly higher in CRC patients compared to those with adenomas or non-tumor lesions. Fecal SDC2 Ct value alone yielded an AUC of 0.814 (95% CI, 0.751-0.876). The AUC increased to 0.866 (95% CI, 0.814-0.918) after addition of CEA and to 0.872 (95% CI, 0.818-0.926) for the full model incorporating CEA, CA19-9, CA242, and CA50. At the Youden-optimal threshold, the full model achieved a sensitivity of 87.3% (95% CI, 76.0%-93.7%), specificity of 78.6% (95% CI, 73.6%-82.9%), PPV of 42.9% (95% CI, 34.1%-52.1%), and NPV of 97.1% (95% CI, 94.2%-98.6%). In contrast, individual serum markers showed limited diagnostic performance, with AUC values of 0.709 (CEA), 0.666 (CA19-9), 0.495 (CA242), and 0.567 (CA50). Conclusion: Integration of fecal SDC2 Ct values with serum tumor markers showed a modest improvement in the noninvasive discrimination of CRC compared with SDC2 alone. Prospective external and stage-specific validation is required before clinical screening implementation.
SN - 2234-943X
ER -