Fig. 6.

CREB signaling predicts ADT-resistance and metastatic progression in PCa patients. A Representative IHC images and boxplots representing protein expression of CREB in nuclear stainings detected by IHC in normal-like glands or tumor cells in PCa patient TMAs (n = 83). B Kaplan–Meier analysis of BCR-free survival ratio based on CREB protein expression in a panel of 59 PCa patients (PSA $\ge$ 0.2 ng/L). C Association of CREB expression at predicting time to biochemical recurrence of high/low-risk disease in the resection cohort. Reduced progression-free survival in months of the “high-risk” subgroup (blue) of 161 patients when compared with the “low-risk” subgroup (red) of 161 patients (HR = 1.56 [1.13–2.16]; p < 0.0073). D Association of CREB expression at predicting time to metastatic disease recurrence of high/low-risk disease in the resection cohort. Reduced progression-free survival in months of the “high-risk” subgroup (red) of 161 patients compared with the “low-risk” subgroup (blue) of 161 patients (HR = 2.09 [1.15–3.83]; p < 0.0164). HR = hazard ratio. (E) LNCaP xenograft model was serially passaged in castrated NSG males. WB analysis of AR, p-CREB, CREB, STAT3 protein expression in LNCAP AD/AI tumors. β-actin serves as a loading control