Immune Cell Infiltration and Causal Relationships with Prostate Cancer: A Transcriptomic and Mendelian Randomization Study
Categoría del artículo: Research Article
Publicado en línea: 17 sept 2025
Recibido: 12 dic 2024
Aceptado: 26 jun 2025
DOI: https://doi.org/10.2478/fco-2024-0012
Palabras clave
© 2025 Haishu Xu et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Background
Prostate cancer (PCa) is a significant health concern, with immune cell infiltration playing a crucial role in its pathogenesis. Understanding the immune landscape of prostate tumors compared to healthy tissue is essential for developing novel therapeutic strategies. This study aims to estimate immune cell infiltration in prostate tumors and healthy tissues and investigate the causal relationships between immune phenotypes and PCa using Mendelian randomization.
Methods
Transcriptomic data from The Cancer Genome Atlas was utilized to compare prostate tumor tissues with healthy controls. Immune cell infiltration was estimated using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts, single-sample Gene Set Enrichment Analysis, and xCell methodologies. Mendelian randomization was employed to explore causal relationships between 731 immune phenotypes and PCa, using five methods including inverse-variance weighting for evaluation. Results with a false discovery rate (FDR)-adjusted P-value <0.05 were considered significant. Sensitivity analyses, including heterogeneity tests, pleiotropy tests, and leave-one-out analyses, were conducted to ensure the robustness of the findings.
Results
Significant differences in the infiltration of macrophages, neutrophils, and basophils were observed between prostate tumors and healthy tissues. Before FDR correction, 42 immune phenotypes showed a causal relationship with PCa. After FDR correction, CD4 on HLA DR+ CD4+ T cells exhibited a significant causal association with PCa (odds ratio [95% confidence interval] = 0.54 (0.43–0.71), P = 3.86E-06). Sensitivity analyses revealed no abnormalities, confirming the reliability of the results.
Conclusions
This study highlights the significant differences in immune cell infiltration between PCa and healthy tissues and identifies a causal relationship between specific immune phenotypes and PCa. The findings provide valuable insights for future research and potential therapeutic targets in PCa treatment.