Circulating cfDNA promoter methylation: An emerging biomarker for early detection of advanced adenoma and colorectal cancer

Cell-free DNA (cfDNA) methylation has emerged as a promising avenue for the early detection of various cancers. However, specific biomarkers for advanced adenoma (AA) and colorectal cancer (CRC) are yet to be fully characterized. This study aimed to investigate the potential of circulating cfDNA promoter methylation as a non-invasive biomarker for the diagnosis of AA and CRC. We identified methylation-driven genes using The Cancer Genome Atlas data comprising 5,892 tumor-normal pairs, and subsequently analyzed plasma cfDNA from 307 participants by employing quantitative methylation-specific PCR to validate the methylation status of the miR-129-2 promoter (Clinical Trial Registration: ChiCTR2400080025). The diagnostic performance revealed significant elevation of cfDNA miR-129-2 promoter methylation in AA and CRC patients compared to healthy controls, surpassing conventional markers such as CEA and CA199. Additionally, next-generation sequencing demonstrated a robust correlation between mutation frequency and methylation (R=0.978, P