Cell-free DNA methylation and fragmentomics-based liquid biopsy for accurate esophageal cancer detection

Background: Cell-free DNA is a promising source of biomarkers for early cancer detection and carries tumor-driven methylation and fragmentation features that have achieved good diagnostic efficacy across various cancers. However, there were no studies that detected both of them for esophageal cancer diagnosis. 

Methods: In this study, we analyzed the cfDNA methylation and fragmentation markers for accurate esophageal cancer detection. Using cfMeDIP-seq, we profiled 145 plasma samples from healthy controls and esophageal cancer patients. We used multiple algorithms to identify cfDNA methylation markers and fragmentation markers to evaluate the efficacy of early esophageal cancer detection. 

Results: Finally, we identified 25 cfDNA methylation and fragmentation markers and constructed a machine-learning model, which achieved a sensitivity of 99% and specificity of 97.82% in an independent cohort. These results indicate that methylation and fragmentomics biomarkers based on cfMeDIP-seq can accurately distinguish esophageal cancer patients from non-tumor controls. 

Conclusion: Our study based on cfMeDIP-seq highlights the efficacy of cfDNA methylation and fragmentation histology markers in diagnosing esophageal cancer and provides a direction for subsequent research.