Landscape of Prostate-Specific Membrane Antigen Heterogeneity in Metastatic Prostate Cancer [ChIP-Seq]

Prostate-specific membrane antigen (PSMA) has emerged as an important therapeutic target in metastatic castration-resistant prostate cancer (CRPC). However, not all patients respond to PSMA-targeted therapy, in part due to heterogeneity of tumor expression of the target PSMA. Furthermore, loss of PSMA expression develops in up to 15-20% of patients with CRPC, and the underlying mechanisms remain poorly defined. In this study,To investigate possible epigenetic regulation of PSMA in the context of HOXB13-independent PSMA-suppressed tumors, we performed ChIPseq to evaluate the activation mark Histone H3 Lysine 27 acetylation (H3K27ac) on our previously characterized organoids. Similar to AR-positive, PSMA-positive 22Rv1 cells, the AR-negative, PSMA-positive NEPC model WCM1262 demonstrated H3K27ac at the PSMA (FOLH1) gene promotor corresponding with high PSMA expression, whereas other PSMA-negative NEPC models demonstrated low H3K27ac. Overall design: We performed H3K27ac ChIPseq on 22Rv1 cell line and our previously NEPC organoids including WCM154, WCM155, WCM 1078 and WCM1262.