| HRA006113
(Controlled Access)
|
Detecting early-stage esophageal squamous cell carcinoma (ESCC) and precancerous lesions is critical for improving survival. Here, we conducted whole-genome bisulfite sequencing (WGBS) in 460 cfDNA samples of no-metastatic ESCC or precancerous lesions and matched healthy controls from multicenter. We developed an expanded multimodal analysis (EMMA) framework to simultaneously identify cfDNA methylation, copy number variants (CNVs), and fragmentation markers in cfDNA WGBS data. EMMA significantly improved the detection rate, increasing AUCs from 0.90 to 0.99, and detected 87% of ESCCs and 62% of precancerous lesions with >95% specificity in validation cohorts. Our findings demonstrate the potential of multimodal analysis of cfDNA methylome for ultra-early ESCC detection and monitoring of molecular characteristics. |
