Early prediction of minimal residual disease in colorectal cancer via SEPTIN9 methylation status in circulating tumor DNA

Objective Minimal residual disease (MRD) is a major cause of postoperative recurrence in colorectal cancer (CRC), significantly impacting survival outcomes. This study aimed to evaluate the methylation status of the SEPTIN9 gene (mS9) in circulating tumor DNA (ctDNA) as a biomarker for detecting MRD and predicting recurrence in post-surgery CRC patients.Methods In this retrospective, single-center analysis, we evaluated mS9 in ctDNA as a biomarker for postoperative recurrence among 68 patients with stage I-IV CRC. The inclusion of stage IV patients is notable, as it substantially affects the overall recurrence risk profile of the cohort. Plasma samples collected after curative resection were analyzed for mS9 via real-time quantitative PCR, and its association with recurrence-free survival (RFS) was retrospectively examined.Results Postoperative mS9 positivity in ctDNA was significantly associated with reduced RFS. Patients with mS9-positive in ctDNA one month after surgery exhibited markedly shorter RFS than those who were mS9-negative. Additionally, mS9 positivity was correlated with a higher recurrence risk both in early and long-term postoperative stages, demonstrating superior predictive performance to carcinoembryonic antigen (CEA).Conclusion ctDNA mS9 can serve as an effective non-invasive biomarker for MRD detection and showed stronger recurrence-risk stratification than CEA in this cohort. The combination of mS9 and CEA further enhances prognostic accuracy for CRC patients.