Characterization of DNA methylation patterns in early‑stage NSCLC

DNA methylation is a central regulator of gene expression and a well-recognized contributor to tumorigenesis, but methylation profiling in stage I disease has largely relied on array-based platforms with limited genomic coverage. Here we systematically characterized the DNA methylation landscape of stage I lung cancer at base resolution.

We first identified differentially methylated regions (DMRs) distinguishing stage I tumors from adjacent normal lung tissue, and compared these with alterations observed at later stages. We then examined the functional consequences of these DMRs by testing their associations with differential gene expression, thereby linking epigenetic alterations to transcriptional dysregulation in early disease. Finally, we mapped regions of coordinated methylation (co-methylation) and assessed their relationship with cancer-associated gene dysregulation, with the aim of identifying epigenetically regulated gene networks that operate from the earliest detectable stage of tumorigenesis.