LINE-1 cfDNA Methylation as an Emerging Biomarker in Solid Cancers

Abstract

Epigenetic dysregulation is a hallmark of many human malignancies, with DNA methylation being a primary mechanism influencing gene expression and maintaining genomic stability. Genome-wide hypomethylation, characteristic of many cancers, is partly attributed to the demethylation of repetitive elements, including LINE-1, a prevalent non-LTR retrotransposon. The methylation status of LINE-1 is closely associated with overall genomic methylation levels in tumors. cfDNA comprises extracellular DNA fragments found in bodily fluids such as plasma, serum, and urine, offering a dynamic snapshot of the genetic and epigenetic landscape of tumors. This real-time sampling provides a minimally invasive avenue for cancer diagnostics, prognostics, and monitoring. The methylation status of LINE-1 in cfDNA has emerged as a promising biomarker, with several studies highlighting its potential in diagnosing and predicting outcomes in cancer patients. Recent research also suggests that cfDNA-based LINE-1 methylation analysis could serve as a valuable tool in evaluating the efficacy of cancer therapies, including immunotherapy. The growing clinical significance of cfDNA calls for a closer examination of its components, particularly repetitive elements like LINE-1. Despite their importance, the role of LINE-1 elements in cfDNA has not been thoroughly gauged. We aim to address this gap by reviewing the current literature on LINE-1 cfDNA assays, focusing on their potential applications in diagnostics and disease monitoring.