Xiao Lin, Wu Tianen
Department of Urology, Jinjiang Municipal Hospital, Quanzhou, 362200, Fujian Province, China.
Discov Oncol. 2025 May 24;16(1):912. doi: 10.1007/s12672-025-02757-z.
While testicular cancer is highly curable, drug resistance remains a challenge in relapsed or refractory cases. This study explores the immune system's role in resistance mechanisms via bidirectional Mendelian Randomization (MR) analysis of 731 immune cell phenotypes.
We conducted a two-sample bidirectional MR analysis using IVW, MR-Egger, weighted median, and other models, leveraging public genetic datasets. Sensitivity analyses were performed to ensure robustness and assess pleiotropy.
The MR analysis revealed 12 immune cell phenotypes causally linked to testicular cancer development and 16 phenotypes significantly modulated by the disease, highlighting potential therapeutic resistance mechanisms. Several identified immune markers were associated with known drug resistance pathways, suggesting novel therapeutic targets. Sensitivity analyses confirmed the robustness of our primary findings and their relevance to drug resistance mechanisms.
Our findings reveal immune-related mechanisms underlying drug resistance in testicular cancer, offering potential targets for overcoming therapeutic resistance and guiding future treatment strategies.
虽然睾丸癌的治愈率很高，但耐药性在复发或难治性病例中仍然是一个挑战。本研究通过对731种免疫细胞表型进行双向孟德尔随机化（MR）分析，探讨免疫系统在耐药机制中的作用。
我们利用公开的遗传数据集，使用IVW、MR-Egger、加权中位数和其他模型进行了两样本双向MR分析。进行敏感性分析以确保稳健性并评估多效性。
MR分析揭示了12种与睾丸癌发生有因果关系的免疫细胞表型，以及16种受该疾病显著调节的表型，突出了潜在的治疗耐药机制。几个确定的免疫标志物与已知的耐药途径相关，提示了新的治疗靶点。敏感性分析证实了我们主要发现的稳健性及其与耐药机制的相关性。
我们的研究结果揭示了睾丸癌耐药性背后的免疫相关机制，为克服治疗耐药性和指导未来治疗策略提供了潜在靶点。
