Fig. 3
EDARADD is hypomethylated in CAFs from high-grade group prostate cancer. a Schematic of genes proximal to Gleason-DMRs in CAFs from GG ≤ 3 versus GG ≥ 4 prostate cancer. Gleason-DMRs that are hypermethylated in GG ≥ 4 CAFs are shown in green, while Gleason-DMRs that are hypomethylated in GG ≥ 4 CAFs are shown in purple. Seven of these Gleason-DMRs were also differentially methylated in GG ≥ 4 CAFs versus all other groups of fibroblasts (see panel b). Of these Gleason-DMRs, EDARADD was also significantly differentially methylated in GG ≥ 4 versus GG ≤ 3 tissues from TCGA (see panel c). b Boxplots showing DNA methylation of Gleason-DMRs in different groups of fibroblasts. Each dot represents a different fibroblast sample (*P < 0.05 One-way ANOVA GG ≥ 4 CAF vs all other groups). c Plot of EDARADD DNA methylation levels in patient tissue samples from TCGA. Samples are arranged as GG ≤ 3 versus GG ≥ 4 prostate cancer (aP = 8.3 × 10−5, diff = − 5.2%, Mann-Whitney test) and as individual grade groups. Each dot represents a different patient, with lines indicating median and ± IQR. d Schematic of the EDARADD Gleason-DMR showing the levels of DNA methylation at each CpG site in each CAF (blue = low methylation; red = high methylation). The trend lines show the average methylation status of GG ≤ 3 CAFs (light blue) versus GG ≥ 4 CAFs (orange). The location of the Gleason-DMR is shown in purple