TET3 is expressed in prostate cancer tumor‑associated macrophages and is associated with anti‑androgen resistance

• Qiu ju Wei ^[1] ; Hai qi Liang ^[1] ; Yao wen Liang ^[2] ; Zu xin Huang ^[2]
  1. [1] Guangxi Medical University

     Guangxi Medical University

     China

     
  2. [2] Department of Urology, The First Afliated Hospital of Guangxi Medical University, Nanning, China
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 27, Nº. 4, 2025, págs. 1712-1727
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Purpose The aim of this study is to investigate the expression of TET3 in prostate cancer and its efect on the efcacy of anti-androgen therapy (ADT).

    Methods The expression of TET3 in 1965 cases of prostate cancer and 493 cases of normal prostate tissues were analyzed. The CIBERSORT algorithm evaluated the abundance of 22 tumor-infltrating immune cells in 497 prostate cancers. Subsequently, the expression of TET3 in prostate cancer TAMs was analyzed using 21,292 cells from single-cell RNA sequencing (scRNAseq). In addition, the trajectory of the diferentiation process was reconstructed based on pseudotime analysis.

    Sensitivity prediction of prostate cancers to ADT was evaluated based on GDSC2 and CTRP databases. Another dataset GSE111177 was employed for further analysis.

    Results TET3 was over-expressed in prostate cancer, and the expression of TET3 in metastatic prostate cancer was higher than that in non-metastatic prostate cancer. The scRNAseq analysis of prostate cancer showed that TET3 was mainly expressed in TAM. TET3 expressed in early and active TAMs, with the activation of signaling pathways such as energy metabolism, cell communication, and cytokine production. Prostate cancer in TET3 high expression group was more sensitive to ADT drugs such as Bicalutamide and AZD3514, and was also more sensitive to chemotherapy drugs such as Cyclophosphamide, Paclitaxel, and Vincristine, and MAPK pathway inhibitors of Docetaxel and Dabrafenib.

    Conclusions The efcacy of ADT in prostate cancer is related to the expression of TET3 in TAMs, and TET3 may be a potential therapeutic target for coordinating ADT.