Fig. 4

EDARADD expression is increased in high-grade prostate cancer and correlated with DNA methylation. a Plot showing the average expression of EDARADD (± SEM) in each group of NPFs (blue) and CAFs (red). There was significantly higher mRNA abundance in ≥ GG4 CAFs versus each other fibroblast group (**P < 0.01 One-way ANOVA with Tukey post hoc analysis). b Scatter plot showing the significant negative correlation between EPIC data for EDARADD DNA methylation and qRT-PCR data for EDARADD mRNA abundance (Spearman correlation, P < 0.0001). Each dot represents a different fibroblast sample. c Plot of RNA-seq data showing higher EDARADD expression in ≥ GG4 versus ≤ GG3 prostate cancer specimens from TCGA (b logFC between GG1-3 vs GG4-5 = 1.57, genome-wide adjusted P = 6.9 × 10⁻⁰⁷, generalized linear model using edgeR). d Scatter plot of matching EDARADD 450K DNA methylation data and RNA-seq data from TCGA showing a significant negative correlation (Spearman correlation, P = 3.2 × 10¹⁷). e Representative images of immunohistochemistry (IHC) for EDARADD in matched benign and tumour tissues. Scale bars equal 50 μm. f Plot of the average EDARADD stromal IHC score (± SEM) in each group of patient tissues. There was significantly higher EDARADD staining in ≥ GG4 tumours versus ≤ GG3 tumours and benign samples (*P < 0.05, **P < 0.01 One-way ANOVA with Tukey post hoc analysis). g Scatter plot showing the significant negative correlation between EDARADD DNA methylation in fibroblasts and the stromal EDARADD IHC score in matching patient tissues (Spearman correlation, P = 0.0006)