To summarize the biological basis, technical platforms, clinical evidence, and challenges of methylation-based multi-cancer early detection (MCED) using liquid biopsy, emphasizing the importance of clinical translation.
Approach:
Key Findings:
CCGA study demonstrated 99.3% specificity and 67.3% sensitivity for early-stage cancers.
PATHFINDER study showed a positive predictive value of approximately 38% in a real-world screening context.
SYMPLIFY study achieved a positive predictive value of 75.5% and a negative predictive value of 97.6% in symptomatic populations.
Interpretation:
Methylation-based liquid biopsy techniques show promise for early cancer detection, but clinical translation faces challenges such as standardization, cost, and biological confounding factors.
Limitations:
Technical standardization remains a challenge.
Biological confounding factors may affect assay performance, such as variations in cfDNA shedding.
High costs and the need for large-scale prospective validation hinder widespread adoption.
Conclusion:
Methylation liquid biopsy has the potential to transform cancer screening from late diagnosis to early intervention, contributing to precision oncology, but further research and validation are necessary.
