TGF-β1/TRAF-6 and IL-6/STAT-3 pathways in PSA-PSMA phenotypes of hormone-sensitive and hormone-refractory prostate Cancer.

This study explored the relationship between systemic cytokines and PSA-PSMA phenotypes in benign prostatic hyperplasia (BPH) and prostate cancer (PCa), including hormonal therapy response. Serum cytokines (IL-6, TNF-α, IL-10, IL-17 A, TGF-β1) and PSA were quantified, while tissue PSA, PSMA, CD34, TRAF-6, and phosphorylated STAT3 (Ser727, Tyr705) were evaluated immunohistochemically. AR and AR-V7 mRNA expression were assessed by RT-PCR. PCa patients exhibited elevated IL-6 and TGF-β1, higher PSMA and CD34, and reduced tissue PSA compared to BPH. pSTAT3 (Tyr705) increased, whereas pSTAT3 (Ser727) decreased in PCa. In hormone-refractory PCa, TGF-β1 and PSMA were elevated, while PSA declined. AR-V7 was largely absent, and TRAF-6 showed no hormonal difference. These findings suggest IL-6/STAT3 and TGF-β1/TRAF-6 pathways modulate PSA-PSMA dynamics, with TGF-β1/TRAF-6 particularly linked to hormone-refractory progression. Cytokine-mediated signaling may inform PCa diagnosis, prognosis, and therapeutic targeting.