Taken together, our results suggested that low promoter methylation levels of certain AR-regulated genes (i.e. SLC45A3, STEAP2, ELK4 and TMPRSS2) may contribute to the AR-driven tumor phenotype seen in the majority of CRPC patients with metastatic disease [2–12], while high promoter methylation of the same genes may contribute to the development of less AR-dependent CRPC, commonly referred to as AR-indifferent, small-cell or neuroendocrine-like CRPC [41]. Here, TMPRSS2 is linked to metastatic neoplasm.