Abstract

Background: The unprocessed precursor of brain-derived neurotrophic factor (BDNF), proBDNF, has emerged as a potential determinant of therapeutic response in prostate cancer. Upon secretion, proBDNF preferentially binds to the co-receptors sortilin and p75NTR, triggering pro-apoptotic or pro-survival cascades, depending on cellular context. ProBDNF engages sortilin/p75NTR to drive castration resistance and metastasis in prostate cancer. High proBDNF/sortilin predicts poor therapy outcome, yet their tissue expression in prostate cancer (PCa) remains unclear.
Methods: To evaluate the protein expression levels of proBDNF, sortilin, and p75NTR, we performed immunohistochemical analyses on 18 formalin-fixed paraffin-embedded (FFPE) PCa tissues obtained at radical prostatectomy between 2024 and 2025, together with matched para-carcinoma tissues.
Results: Compared with para-carcinoma tissues, immunohistochemistry in 18 paired specimens showed that pro-BDNF was significantly upregulated in PCa tissues (median IHC score 60.5 (range 57 - 65) vs. 41.5 (40 - 45), p < 0.05). Sortilin expression was also higher in PCa (median 37.0 (35 - 39) vs. 16.5 (15 - 18), p < 0.01); P75 expression remained relatively low in both prostate cancer and adjacent non-cancerous tissues (18.5 (17 - 20) vs. 6.5 (5 - 8), p < 0.05).
Conclusions: These findings suggest a correlation between the expression levels of proBDNF, sortilin, and p75-NTR and the characteristics of PCa. Further investigation into the mechanisms underlying these interactions may provide valuable insights for the development of targeted therapies for PCa.

DOI: 10.7754/Clin.Lab.2025.250618