代谢物介导的免疫调节失衡与骨骼和关节软骨的恶性肿瘤的发生之间的关系：孟德尔随机研究
The relationship between metabolite mediated immune regulatory imbalance and the occurrence of malignant tumors of bone and articular cartilage: a Mendelian randomization study
影响因子:5.90000
分区:医学2区 / 免疫学2区
发表日期:2024
作者:
Kehan Long, Ao Gong, Tengfei Zheng, Shoushen Liu, Zhendong Ying, Cong Xiao
摘要
这项研究旨在评估骨骼和关节软骨的免疫细胞特征与恶性肿瘤之间的因果关系，重点是代谢物的介导作用。使用孟德尔随机化，我们根据遗传变异评估了这些关系，以识别潜在的生物标志物和治疗靶标。使用GWAS数据进行了一次免疫细胞特征和1,400代谢物研究直接和介导效应的两个样本Mendelian随机分析。使用R软件执行有效的仪器变量（IVS），并使用R软件进行统计分析，包括逆差异加权（IVW），加权中位数和基于模式的方法。这种方法能够评估直接因果关系，以及代谢产物在免疫细胞特征和恶性肿瘤之间关联中的潜在中介作用。在26种免疫表型和骨骼和关节软骨的恶性肿瘤之间鉴定了显着的因果关系。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有正相关。进一步的分析表明，与67个代谢产物的因果关系，其中38个呈正相关，而29个负相关。调解分析强调了免疫监测和代谢失调在肿瘤发育中的作用，这是由免疫表型SSC-A对HLA DR+ NK细胞上的免疫表型之间的关联证明的，而代谢物5-羟基己酸盐的作用。关系。这些见解为进一步的研究奠定了基础，并可能有助于发展新的生物标志物和治疗策略。
Abstract
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.