Overall, our results suggest key mechanisms involved in PCa development in this high-risk subgroup, including upregulated signatures of negative AR regulation through AGR3 hypermethylation and IRF2BP1-EAP1 hypomethylation, downregulation of tumor suppressor genes (BTG2 and DKK3), and activation of the Wnt/β-catenin pathway via AGR3 hypermethylation and DKK3, HIC1 hypomethylation. This evidence concerns the gene IRF2BP1 and posterior cortical atrophy.