Circulating tumor DNA methylation-based method for noninvasive detection and stage stratification of colorectal tumor.

Summary

This prospective study developed a 21-marker ctDNA methylation panel that achieved 87.82% sensitivity and 91.88% specificity for detecting advanced adenomas and CRC, outperforming conventional tumor markers. A second model stratified early versus advanced disease to inform curative endoscopic resection decisions, with overall accuracy exceeding 83%.

Key Findings

• Identified 4,965 differential ctDNA methylation biomarkers and distilled a 21-marker panel via shrinkage.
• Diagnostic model (cMCD) achieved 87.82% sensitivity and 91.88% specificity; accuracy 89.85%, outperforming CEA, CA19-9, and CA72-4 (all P < 0.001).
• Stage stratification model (cMCSS) discriminated 75.86% of Early-stage and 89.45% of Advanced-stage patients with 83.42% accuracy.

Clinical Implications

Could augment or replace serum tumor markers in CRC workups, enabling earlier detection of advanced adenomas and tailoring intervention (e.g., selecting patients for curative endoscopic resection).

Limitations

• External multi-center validation and health-economic assessment are not reported.
• Potential population or platform-specific biases may affect generalizability.

Future Directions

External validation across diverse populations, assay standardization, integration with imaging/clinical predictors, and prospective utility studies in screening pathways.