免疫细胞与泌尿系统恶性肿瘤之间的因果关系:双向孟德尔随机化研究
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海市2024“科技创新行动计划”新星计划(24YF2758900)


Causal relationship between immune cells and urological malignancies: a bidirectional Mendelian randomization study
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Supported by Shanghai 2024 "Scientific and Technological Innovation Action Plan" Rising Star Program (24YF2758900)

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    摘要:

    目的 采用孟德尔随机化(MR)和反向MR探讨731种免疫细胞表型与前列腺癌、膀胱癌和肾癌之间的潜在因果关系。方法 从全基因组关联研究数据库提取免疫细胞、前列腺癌、膀胱癌和肾癌的汇总统计数据,采用两样本MR分析评估731种免疫细胞表型与前列腺癌、膀胱癌和肾癌之间的因果关系。主要分析采用逆方差加权(IVW)法,并采用错误发现率(FDR)法对IVW法的P值进行多重校正;利用敏感性分析评估主要结果的稳健性。最后,通过反向MR分析以探索反向因果关系。结果 IVW法表明46种免疫细胞表型与前列腺癌相关(23个保护性特征和23个危险性特征),34种免疫细胞表型与肾癌相关(17个保护性特征和17个危险性特征),38种免疫细胞表型与膀胱癌相关(18个保护性特征和20个危险性特征)。通过FDR法多重校正后,4种免疫细胞表型[IgD+CD24+ B细胞水平、CD24+CD27+淋巴细胞水平、人类白细胞抗原(HLA)DR+ T细胞绝对细胞计数水平和CD16-CD56+自然杀伤细胞水平]与前列腺癌风险有关,4种免疫细胞表型(IgD+CD38-淋巴细胞水平、CD127-CD8bright T细胞绝对细胞计数水平、CD11c+髓样树突状细胞水平和HLA DR+ B细胞水平)与肾癌风险有关(均FDR<0.3)。反向MR分析在前列腺癌和肾癌与上述免疫细胞之间未发现阳性结果。结论 免疫细胞与前列腺癌和肾癌之间有潜在因果关系。这可能为探索泌尿系统恶性肿瘤的早期筛查策略和生物学机制提供新的方向,对开发更有效的免疫疗法至关重要。

    Abstract:

    Objective To explore the potential causal associations between 731 immune-cell phenotypes and urological malignancies (prostate cancer, bladder cancer, and kidney cancer) using Mendelian randomization (MR) and reverse MR. Methods Summary statistics for immune cells, prostate cancer, bladder cancer, and kidney cancer were collected from the Genome-Wide Association Study database. A two-sample MR analysis was performed to assess the causal relationships between 731 immune-cell phenotypes and prostate cancer, bladder cancer, and kidney cancer. The inverse variance weighted (IVW) method was used for the primary analysis, and the corresponding P values were subjected to multiple-testing corrections using the false discovery rate (FDR). Sensitivity analyses were conducted to evaluate the robustness of the main findings. Finally, reverse MR analysis was performed to explore potential reverse causality. Results The IVW method identified 46 immune-cell phenotypes associated with prostate cancer (23 protective and 23 risk), 34 with kidney cancer (17 protective and 17 risk), and 38 with bladder cancer (18 protective and 20 risk). After multiple-testing correction using the FDR, 4 immune-cell phenotypes (immunoglobulin [Ig]D+CD24+ B cell level, CD24+CD27+ lymphocyte level, human leukocyte antigen [HLA] DR+ T cell absolute count level, and CD16CD56+ natural killer cell level) showed significant associations with prostate cancer risk, and 4 immune-cell phenotypes (IgD+CD38 lymphocyte level, CD127 CD8bright T cell absolute count level, CD11c+ myeloid dendritic cell level, and HLA DR+ B cell level) showed significant associations with kidney cancer risk (all FDR < 0.3). The reverse MR analysis found no positive results between prostate cancer or renal cell carcinoma and the aforementioned immune cells. Conclusion There are potential causal relationships between immune cells and both prostate cancer and kidney cancer, which may provide new directions for exploring early screening strategies and biological mechanisms for urological malignancies, and is also crucial for developing more effective immunotherapies.

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  • 收稿日期:2025-03-18
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  • 在线发布日期: 2026-02-12
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