Abstract
With the increased awareness of early tumor detection, the importance of detecting and diagnosing esophageal cancer in its early stages has been underscored. Studies have consistently demonstrated the crucial role of methylation levels in circulating cell-free DNA (cfDNA) in identifying and diagnosing early-stage cancer. cfDNA methylation pertains to the methylation state within the genomic scope of cfDNA and is strongly associated with cancer development and progression. Several research teams have delved into the potential application of cfDNA methylation in identifying early-stage esophageal cancer and have achieved promising outcomes. Recent research supports the high sensitivity and specificity of cfDNA methylation in early esophageal cancer diagnosis, providing a more accurate and efficient approach for early detection and improved clinical management. Accordingly, this review aims to present an overview of methylation-based cfDNA research with a focus on the latest developments in the early detection of esophageal cancer. Additionally, this review summarizes advanced analytical technologies for cfDNA methylation that have significantly benefited from recent advancements in separation and detection techniques, such as methylated DNA immunoprecipitation sequencing (MeDIP-seq). Recent findings suggest that biomarkers based on cfDNA methylation may soon find successful applications in the early detection of esophageal cancer. However, large-scale prospective clinical trials are required to identify the potential of these biomarkers.