Analysis of LINE-1 DNA Methylation in Colorectal Cancer, Precancerous Lesions, and Adjacent Normal Mucosa

Background and Objectives: Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide. Genetic and epigenetic changes, especially DNA methylation alterations, are key in CRC development. LINE-1 hypomethylation marks global DNA methylation loss and genomic instability, making it a potential early CRC biomarker. This study investigates the methylation status of LINE-1 in colorectal adenocarcinoma, precancerous lesions (tubular and serrated adenomas), and the surrounding normal mucosa, aiming to elucidate its role as an epigenetic marker in early colorectal tumorigenesis. Materials and Methods: Paired lesion and normal tissue samples from 66 patients were analyzed for LINE-1 methylation at three CpG sites using bisulfite pyrosequencing. Results: Adenocarcinomas and tubular adenomas showed significant hypomethylation, especially at loci A and B, while serrated adenomas exhibited no significant differences. Conclusions: LINE-1 hypomethylation is associated with colorectal tumorigenesis, with distinct patterns observed between tubular and serrated adenomas, indicating distinct pathways forming and progressing specific adenomas. These findings support the potential of LINE-1 methylation as an early epigenetic biomarker for CRC risk stratification and highlight the need for further research into its clinical utility.