Unraveling drug resistance mechanisms in testicular cancer through immune cell phenotypes: a bidirectional Mendelian randomization analysis revealing novel therapeutic targets.

OBJECTIVE

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.

METHOD

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.

RESULTS

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.

CONCLUSION

Our findings reveal immune-related mechanisms underlying drug resistance in testicular cancer, offering potential targets for overcoming therapeutic resistance and guiding future treatment strategies.