Department of Orthopedics, The Third Hospital of Mianyang· Sichuan Mental Health Center, Mianyang, China.
Department of Orthopedics, Second Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Front Immunol. 2024 Aug 9;15:1433219. doi: 10.3389/fimmu.2024.1433219. eCollection 2024.
This study aims to assess the causal relationship between immune cell characteristics and malignant tumors of bone and articular cartilage, focusing on the mediating role of metabolites. Using Mendelian randomization, we evaluated these relationships based on genetic variations to identify potential biomarkers and therapeutic targets.
A two-sample Mendelian randomization analysis was conducted using GWAS data for immune cell features and 1,400 metabolites to investigate direct and mediating effects. Effective instrumental variables (IVs) were selected, and statistical analyses-including inverse variance weighting (IVW), weighted median, and mode-based methods-were performed using R software. This approach enabled the assessment of direct causal relationships as well as the potential mediating role of metabolites in the association between immune cell features and malignancies.
Significant causal relationships were identified between 26 immune phenotypes and the risk of malignant tumors of bone and articular cartilage. Notably, the HLA DR+ NK cell phenotype SSC-A showed a positive correlation with the risk of these malignancies. Further analysis revealed causal relationships with 67 metabolites, 38 of which were positively correlated and 29 negatively correlated. Mediation analysis highlighted the role of immune surveillance and metabolic dysregulation in tumor development, as evidenced by the association between the immune phenotype SSC-A on HLA DR+ NK cells and the metabolite 5-hydroxyhexanoate.
The findings suggest significant causal relationships between immune phenotypes and malignant tumors of bone and articular cartilage, with metabolites potentially mediating these relationships. These insights lay the groundwork for further research and could contribute to the development of new biomarkers and treatment strategies.
本研究旨在评估免疫细胞特征与骨和关节软骨恶性肿瘤之间的因果关系，重点研究代谢物的介导作用。我们使用孟德尔随机化，基于遗传变异评估这些关系，以确定潜在的生物标志物和治疗靶点。
使用免疫细胞特征和 1400 种代谢物的 GWAS 数据进行两样本孟德尔随机化分析，研究直接和介导作用。选择有效的工具变量（IVs），并使用 R 软件进行统计分析，包括逆方差加权（IVW）、加权中位数和基于模式的方法。这种方法可以评估免疫细胞特征与恶性肿瘤之间关联的直接因果关系以及代谢物的潜在介导作用。
确定了 26 种免疫表型与骨和关节软骨恶性肿瘤风险之间的显著因果关系。值得注意的是，HLA DR+NK 细胞表型 SSC-A 与这些恶性肿瘤的风险呈正相关。进一步的分析揭示了与 67 种代谢物的因果关系，其中 38 种呈正相关，29 种呈负相关。中介分析强调了免疫监视和代谢失调在肿瘤发展中的作用，这一点可以从 HLA DR+NK 细胞上的 SSC-A 免疫表型与 5-羟基己酸酯代谢物之间的关联中得到证明。
这些发现表明免疫表型与骨和关节软骨恶性肿瘤之间存在显著的因果关系，代谢物可能介导这些关系。这些见解为进一步的研究奠定了基础，并可能为新的生物标志物和治疗策略的发展做出贡献。
