Wei Qiu-Ju, Liang Hai-Qi, Liang Yao-Wen, Huang Zu-Xin
Guangxi Medical University, 22 Shuang-Yong Road, Nanning, 530021, Guangxi, China.
Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Clin Transl Oncol. 2025 Apr;27(4):1712-1727. doi: 10.1007/s12094-024-03708-w. Epub 2024 Sep 6.
The aim of this study is to investigate the expression of TET3 in prostate cancer and its effect on the efficacy of anti-androgen therapy (ADT).
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-infiltrating 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 differentiation 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.
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.
The efficacy 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.
本研究旨在探讨TET3在前列腺癌中的表达及其对抗雄激素治疗（ADT）疗效的影响。
分析1965例前列腺癌和493例正常前列腺组织中TET3的表达。CIBERSORT算法评估了497例前列腺癌中22种肿瘤浸润免疫细胞的丰度。随后，使用来自单细胞RNA测序（scRNAseq）的21292个细胞分析前列腺癌TAM中TET3的表达。此外，基于伪时间分析重建了分化过程的轨迹。基于GDSC2和CTRP数据库评估前列腺癌对ADT的敏感性预测。另一个数据集GSE111177用于进一步分析。
TET3在前列腺癌中过表达，转移性前列腺癌中TET3的表达高于非转移性前列腺癌。前列腺癌的scRNAseq分析表明，TET3主要在TAM中表达。TET3在早期和活跃的TAM中表达，伴随着能量代谢、细胞通讯和细胞因子产生等信号通路的激活。TET3高表达组的前列腺癌对比卡鲁胺和AZD3514等ADT药物更敏感，对环磷酰胺、紫杉醇和长春新碱等化疗药物以及多西他赛和达拉非尼的MAPK通路抑制剂也更敏感。
ADT在前列腺癌中的疗效与TAM中TET3的表达有关，TET3可能是协同ADT的潜在治疗靶点。
