Fig. 1: DNA methylation aberrations increase with the progression of precancers.

a Principal component analysis of the methylation profiles of the average methylation values in 39,148 5-kb tiling regions (shared in all samples) composed of autosomal, non-polymorphism CpG sites supported by at least 10× read coverage in IPNs of different stages. The solid dots of different colors represent IPNs of different stages and the star (*) represented the centers of specimens of each histologic stage. b Overall genome-wide DNA methylation correlation between IPNs of different stages and matched normal tissue from the same patients. The yellow-purple clouded dots in the smooth scatter plot represent the CpG sites covered by IPN specimens (n = 14 for AAH, n = 11 for AIS, n = 18 for MIA, n = 10 for ADC) and paired normal lung. Two-tailed Pearson’s correlation coefficient r values are shown on the top. P < 2.2 × 10⁻¹⁶ in all four histologic stages. The red dots represent CpG sites with hypermethylation in IPNs (within DMRs of methylation gain in IPNs and methylation ≤20% of CpG sites in the corresponding normal lung) and the green dots represent CpG sites with hypomethylation (within DMRs of methylation loss in IPNs and methylation ≥20% of CpG sites in the corresponding normal lung). c The number of CpG sites overlapping with DMRs showing hypermethylation (left) or hypomethylation (right) in IPNs of different histologic stages. The green dots represent the mean of normalized numbers of CpG sites overlapping with DMRs in each IPN. The solid blue dots represent the mean numbers of CpG sites overlapping with DMRs in IPNs of each histologic stage with a 95% confidence interval as error bars. The differences among all stages were assessed using the Kruskal–Wallis H test. Source data is provided as a source data file.