Abstract
Development of sensitive biomarkers is required to achieve early detection and tumor burden monitoring in gastric cancer (GC). We performed genome-wide methylation sequencing on 78 tissue and 241 plasma samples from 171 GC patients and 114 healthy controls from two independent clinical centers. Differentially methylated regions (DMRs) were screened using paired GC and normal tissues, and refined through cfDNA profiles with LASSO regression to construct a cfDNA-based biomarker, the GCML-score. The GCML-score, consisting of 13 DMRs, demonstrated excellent diagnostic performance (AUC: 0.95/0.99/0.95 overall and 0.96/0.99/0.82 in early GC for training/internal validation/external validation cohorts). In 12 patients receiving neoadjuvant chemotherapy, dynamic changes in GCML-score were consistent with radiological tumor burden, highlighting its monitoring potential. The GCML-score, derived from genome-wide cfDNA methylation profiling, provides a robust tool for early GC detection and real-time tumor burden monitoring, facilitating improved prognosis and personalized therapeutic strategies.