Fecal DNA SDC2 methylation test for colorectal cancer diagnosis: A systematic review and meta-analysis

Fecal DNA methylation of the syndecan-2 (SDC2) gene is being explored as a noninvasive biomarker for colorectal cancer (CRC) detection. However, its diagnostic performance necessitates thorough evaluation. A systematic search of PubMed, Embase, and Web of Science was conducted to identify studies investigating fecal SDC2 methylation (mSDC2) for CRC diagnosis. Eligible studies included adult CRC patients with histological confirmation and controls with either normal mucosa or benign colorectal lesions. Pooled sensitivity and specificity were synthesized using a Reitsma bivariate random-effects model, and summary receiver operating characteristic (SROC) curves with corresponding area under the curve (AUC) values were derived from this hierarchical model. Twenty-five studies encompassing 3,427 CRC patients, 3,267 individuals with benign lesions, and 5,372 with normal mucosa were included. For the comparison of CRC versus normal mucosa (24 studies), the pooled sensitivity and specificity were 0.86 (95% confidence interval [CI]: 0.82-0.89; I² = 88%) and 0.93 (95% CI: 0.90-0.95; I² = 95%), respectively. The pooled diagnostic odds ratio (DOR) was 81.73 (95% CI: 51.60-129.46), with an AUC of 0.95 (95% CI: 0.93-0.97). In the comparison against benign lesions (22 studies), the sensitivity was 0.85 (95% CI: 0.81-0.89; I² = 87%), specificity was 0.66 (95% CI: 0.59-0.71; I² = 91%), DOR was 11.10 (95% CI: 7.61-16.19), and AUC was 0.83 (95% CI: 0.80-0.86). Deeks' funnel plot asymmetry tests indicated no statistically significant publication bias (p = 0.48 and 0.54). In conclusion, fecal mSDC2 testing demonstrates high diagnostic accuracy for CRC detection when compared to individuals with normal mucosa and moderate performance against benign colorectal lesions. These findings suggest that mSDC2 may serve as a promising noninvasive biomarker to complement existing CRC screening methodologies.