Zhu Linying, Ruan Xiaoyi, Zou Yilun, Ye Shuikang, Xie Liangzhen
School of Obstetrics and Pediatrics, Guangdong Medical University, Zhanjiang, 524023, Guangdong, China.
The First Clinical College, Guangdong Medical University, Zhanjiang, 524023, Guangdong, China.
Discov Oncol. 2025 Jun 19;16(1):1157. doi: 10.1007/s12672-025-02863-y.
Numerous evidence have highlighted a robust association between inflammatory proteins, gut microbiotas, and immune cells and leukemia. However, the causal relationship remains poorly defined. To delve into this connection, we implemented a bidirectional Mendelian randomization (MR) study.
This study utilized genetic variation data from publicly accessible genome-wide association study (GWAS) datasets. We used methods such as inverse variance weighting (IVW) to assess the causal relationship between exposure and the outcome of leukemia. Mediation analyses were applied to investigate the associations between immunophenotypes, gut microbiotas and inflammatory proteins and leukemia. Instrumental variables (IVs) mapping genes were identified, and functional analyses of the related genes were subsequently carried out. Sensitivity analyses was implemented to fortify the robustness of methods and results.
This study uncovered four inflammatory proteins exhibiting significant associations with elevated leukemia risk, while leukemia exerted discernible effects on six inflammatory cytokines. IVW analysis revealed two immune cell subtypes with opposing roles on leukemia risk. One gut microbiota subtypes exhibited a pro-leukemogenic association, contrasted by four subtypes displaying protective influences. Enrichment analysis further identified three differentially expressed genes between malignant and adjacent normal tissues, with related genes demonstrated pronounced pathway enrichment in the mitogen-activated protein kinase (MAPK) signaling pathway.
These findings shed new light on the genetic associations between circulating inflammatory proteins, gut microbiotas, and immune cells and leukemia. It may not only enrich the understanding but also guide deeper clinical and basic research in this domain.
大量证据表明炎症蛋白、肠道微生物群和免疫细胞与白血病之间存在密切关联。然而，因果关系仍不明确。为了深入探究这种联系，我们开展了一项双向孟德尔随机化（MR）研究。
本研究利用了公开可得的全基因组关联研究（GWAS）数据集的基因变异数据。我们使用逆方差加权（IVW）等方法来评估暴露与白血病结局之间的因果关系。应用中介分析来研究免疫表型、肠道微生物群和炎症蛋白与白血病之间的关联。识别出映射基因的工具变量（IVs），随后对相关基因进行功能分析。进行敏感性分析以加强方法和结果的稳健性。
本研究发现四种炎症蛋白与白血病风险升高显著相关，而白血病对六种炎症细胞因子有明显影响。IVW分析揭示了两种对白血病风险起相反作用的免疫细胞亚型。一种肠道微生物群亚型表现出促白血病关联，与之形成对比的是四种显示出保护作用的亚型。富集分析进一步确定了恶性组织与相邻正常组织之间的三个差异表达基因，相关基因在丝裂原活化蛋白激酶（MAPK）信号通路中显示出明显的通路富集。
这些发现为循环炎症蛋白、肠道微生物群和免疫细胞与白血病之间的遗传关联提供了新的见解。这不仅可能丰富对此的理解，还可能指导该领域更深入的临床和基础研究。
