Hu Xinhang, Yu Fenglei, Peng Muyun, Yang Zhi, Ouyang Yifan, Zhang Zhe, Zhao Wangcheng, Yi Xuyang, Hu Huali, Huang Xingchun, Wang Li
Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410000, China.
Thoracic Surgery Research Laboratory, The Second Xiangya Hospital, Central South University, Changsha, 410000, China.
Open Med (Wars). 2025 Apr 15;20(1):20251171. doi: 10.1515/med-2025-1171. eCollection 2025.
Marginal zone lymphoma (MZL) is a rare subtype of non-Hodgkin lymphoma, and its diagnosis primarily relies on pathological biopsy. The study aims to investigate the causal relationships between 41 inflammatory cytokines and MZL using a two-sample bidirectional Mendelian randomization (MR) approach, providing new insights and methodologies for rapid differential diagnosis and treatment strategies.
Causal associations between 41 inflammatory cytokines and MZL were examined using genetic variant data from two large-scale genome-wide association studies. The inverse variance weighting method was employed, and multiple sensitivity analyses, including MR-Egger, weighted median, simple model, and weighted model methods, were conducted to strengthen the robustness of the findings.
Elevated levels of MIG and IL-10 were associated with an increased risk of MZL (MIG: OR = 1.57, = 0.035; IL-10: OR = 1.69, = 0.021), while higher B-NGF levels exhibited a protective effect (OR = 0.46, = 0.027). Reverse MR analysis revealed a negative correlation between MZL and IFN-γ levels (OR = 0.97, = 0.015).
MIG, IL-10, B-NGF, and IFN-γ are potential biomarkers and therapeutic targets for MZL. IFN-γ likely acts as a downstream molecule in MZL pathogenesis, offering novel insights into MZL-related research, clinical diagnosis, and treatment strategies.
边缘区淋巴瘤（MZL）是非霍奇金淋巴瘤的一种罕见亚型，其诊断主要依靠病理活检。本研究旨在采用两样本双向孟德尔随机化（MR）方法探究41种炎性细胞因子与MZL之间的因果关系，为快速鉴别诊断和治疗策略提供新的见解和方法。
利用两项大规模全基因组关联研究的基因变异数据，检验41种炎性细胞因子与MZL之间的因果关联。采用逆方差加权法，并进行包括MR-Egger、加权中位数、简单模型和加权模型方法在内的多种敏感性分析，以增强研究结果的稳健性。
MIG和IL-10水平升高与MZL风险增加相关（MIG：OR = 1.57， = 0.035；IL-10：OR = 1.69， = 0.021），而较高的B-NGF水平具有保护作用（OR = 0.46， = 0.027）。反向MR分析显示MZL与IFN-γ水平呈负相关（OR = 0.97， = 0.015）。
MIG、IL-10、B-NGF和IFN-γ是MZL的潜在生物标志物和治疗靶点。IFN-γ可能在MZL发病机制中作为下游分子发挥作用，为MZL相关研究、临床诊断和治疗策略提供了新的见解。
