白细胞介素 2 受体亚基β作为一种新型枢纽基因，在腹主动脉瘤的免疫微环境中发挥潜在作用。
Interleukin 2 receptor subunit beta as a novel hub gene plays a potential role in the immune microenvironment of abdominal aortic aneurysms.
机构信息
Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
出版信息
Gene. 2022 Jun 15;827:146472. doi: 10.1016/j.gene.2022.146472. Epub 2022 Apr 4.
BACKGROUND
Abdominal aortic aneurysm (AAA) is potentially life threatening and characterized by immune-inflammatory cell infiltration and extracellular matrix degradation. Currently, pharmacotherapy mainly aims to control risk factors without reversion of the dilated aorta. This study analyzed the immune-inflammatory response and identified the immune-related hub genes of AAA.
METHOD
Gene Expression Omnibus datasets (GSE57691, GSE47472 and GSE7084) were downloaded. After identification of GSE57691 differentially expressed genes (DEGs), weighted gene co-expression network analysis of the DEGs was performed. Through enrichment analysis of each module and screening in Immunology Database and Analysis Portal, immune-related hub genes were identified via protein-protein interaction (PPI) network construction and lasso regression. CIBERSORT was utilized to analyze AAA immune infiltration. The correlations between the immune-related hub genes and infiltrating immune cells were investigated. Receiver operating characteristic (ROC) curve analysis was performed to determine immune-related hub gene cutoff values, which were validated in GSE47472 and GSE7084.
RESULT
In GSE57691, 1,018 DEGs were identified. Five modules were identified in the co-expression network. The blue and green modules were found to be related to immune-inflammatory responses, and 61 immune-related genes were identified. PPI and lasso regression analyses identified FOS, IL-6 and IL2RB as AAA immune-related hub genes. CIBERSORT analysis indicated significantly increased infiltration of naive B cells, memory activated CD4 T cells, follicular helper T cells, monocytes and M1 macrophages and significantly decreased infiltration of M2 macrophages in AAA compared with normal samples. IL2RB was more strongly associated with immune infiltration in AAA than were FOS and IL6. The IL2RB area under the ROC curve (AUC) value was > 0.9 in both the training and validation set, demonstrating its strong, stable diagnostic value in AAA.
CONCLUSION
AAA and normal samples had different immune infiltration statuses. IL2RB was identified as an immune-related hub gene and a potential hub gene with significant diagnostic value in AAA.
背景
腹主动脉瘤（AAA）具有潜在的致命性，其特征为免疫炎症细胞浸润和细胞外基质降解。目前，药物治疗主要旨在控制风险因素，而不能逆转扩张的主动脉。本研究分析了 AAA 的免疫炎症反应，并鉴定了免疫相关的枢纽基因。
方法
下载基因表达综合数据集（GSE57691、GSE47472 和 GSE7084）。鉴定 GSE57691 差异表达基因（DEGs）后，对 DEGs 进行加权基因共表达网络分析。通过免疫数据库和分析门户的每个模块的富集分析和筛选，通过构建蛋白-蛋白相互作用（PPI）网络和套索回归来鉴定免疫相关的枢纽基因。利用 CIBERSORT 分析 AAA 的免疫浸润。研究了免疫相关枢纽基因与浸润免疫细胞的相关性。进行接收者操作特征（ROC）曲线分析，以确定免疫相关枢纽基因的截断值，并在 GSE47472 和 GSE7084 中进行验证。
结果
在 GSE57691 中，鉴定出 1018 个 DEGs。在共表达网络中鉴定出 5 个模块。蓝色和绿色模块被发现与免疫炎症反应有关，鉴定出 61 个免疫相关基因。PPI 和套索回归分析鉴定出 FOS、IL-6 和 IL2RB 为 AAA 免疫相关的枢纽基因。CIBERSORT 分析表明，与正常样本相比，AAA 中幼稚 B 细胞、记忆激活的 CD4 T 细胞、滤泡辅助 T 细胞、单核细胞和 M1 巨噬细胞的浸润显著增加，M2 巨噬细胞的浸润显著减少。与 FOS 和 IL6 相比，IL2RB 与 AAA 中的免疫浸润的相关性更强。在训练集和验证集中，IL2RB 的 ROC 曲线下面积（AUC）值均>0.9，表明其在 AAA 中具有较强且稳定的诊断价值。
结论
AAA 和正常样本具有不同的免疫浸润状态。IL2RB 被鉴定为免疫相关的枢纽基因，是 AAA 中具有显著诊断价值的潜在枢纽基因。
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