Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Front Endocrinol (Lausanne). 2024 May 17;15:1390140. doi: 10.3389/fendo.2024.1390140. eCollection 2024.
The aim of this study was to identify potential causal cytokines in thymic malignancies and benign tumors from the FinnGen database using Mendelian randomization (MR).
In this study, data from genome-wide association studies (GWAS) of 91 cytokines were used as exposure factors, and those of thymic malignant tumors and thymic benign tumors were the outcome variables. Two methods were used to determine the causal relationship between exposure factors and outcome variables: inverse variance weighting (IVW) and MR-Egger regression. Sensitivity analysis was performed using three methods, namely, the heterogeneity test, the pleiotropy test, and the leave-one-out test.
There was a causal relationship between the expression of fibroblast growth factor 5, which is a risk factor for thymic malignant tumors, and thymic malignant tumors. C-C motif chemokine 19 expression, T-cell surface glycoprotein CD5 levels, and interleukin-12 subunit beta levels were causally related to thymic malignant tumors and were protective. Adenosine deaminase levels, interleukin-10 receptor subunit beta expression, tumor necrosis factor (TNF)-related apoptosis-inducing ligand levels, and TNF-related activation-induced cytokine levels showed a causal relationship with thymic benign tumors, which are its risk factors. Caspase 8 levels, C-C motif chemokine 28 levels, interleukin-12 subunit beta levels, latency-associated peptide transforming growth factor beta 1 levels, and programmed cell death 1 ligand 1 expression showed a causal relationship with thymic benign tumors, which are protective factors. Sensitivity analysis showed no heterogeneity.
Cytokines showed a causal relationship with benign and malignant thymic tumors. Interleukin-12 subunit beta is a common cytokine that affects malignant and benign thymic tumors.
本研究旨在利用孟德尔随机化（MR）从 FinnGen 数据库中鉴定胸腺癌和良性肿瘤的潜在因果细胞因子。
本研究中，使用了 91 种细胞因子的全基因组关联研究（GWAS）数据作为暴露因素，胸腺癌和胸腺瘤的发生作为结局变量。采用两种方法确定暴露因素与结局变量之间的因果关系：逆方差加权（IVW）和 MR-Egger 回归。使用三种方法（异质性检验、多效性检验和逐一排除检验）进行敏感性分析。
成纤维细胞生长因子 5 的表达与胸腺癌的发生存在因果关系，成纤维细胞生长因子 5 是胸腺癌的危险因素。C-C 基序趋化因子 19 的表达、T 细胞表面糖蛋白 CD5 水平和白细胞介素-12 亚基β水平与胸腺癌的发生存在因果关系，具有保护作用。腺苷脱氨酶水平、白细胞介素-10 受体亚基β表达、肿瘤坏死因子（TNF）相关凋亡诱导配体水平和 TNF 相关激活诱导细胞因子水平与胸腺瘤的发生存在因果关系，是其危险因素。半胱天冬酶 8 水平、C-C 基序趋化因子 28 水平、白细胞介素-12 亚基β水平、潜伏相关肽转化生长因子β1 水平和程序性细胞死亡 1 配体 1 表达与胸腺瘤的发生存在因果关系，是其保护因素。敏感性分析未显示异质性。
细胞因子与良性和恶性胸腺瘤之间存在因果关系。白细胞介素-12 亚基β是一种常见的细胞因子，影响着恶性和良性胸腺瘤。
