Nie Han, Qiu Jiacong, Wen Si, Zhou Weimin
Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Divison of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Genet. 2020 Dec 10;11:579215. doi: 10.3389/fgene.2020.579215. eCollection 2020.
Approximately 13,000 people die of an abdominal aortic aneurysm (AAA) every year. This study aimed to identify the immune response-related genes that play important roles in AAA using bioinformatics approaches. We downloaded the GSE57691 and GSE98278 datasets related to AAA from the Gene Expression Omnibus database, which included 80 AAA and 10 normal vascular samples. CIBERSORT was used to analyze the samples and detect the infiltration of 22 types of immune cells and their differences and correlations. The principal component analysis showed significant differences in the infiltration of immune cells between normal vascular and AAA samples. High proportions of CD4 T cells, activated mast cells, resting natural killer cells, and 12 other types of immune cells were found in normal vascular tissues, whereas high proportions of macrophages, CD8 T cells, resting mast cells, and six other types of immune cells were found in AAA tissues. In the selected samples, we identified 39 upregulated (involved in growth factor activity, hormone receptor binding, and cytokine receptor activity) and 133 downregulated genes (involved in T cell activation, cell chemotaxis, and regulation of immune response mediators). The key differentially expressed immune response-related genes were screened using the STRING database and Cytoscape software. Two downregulated genes, and , and three upregulated genes, , and , were identified by constructing a protein-protein interaction network. Functional enrichment of the differentially expressed genes was analyzed, and the expression of the five key genes in AAA samples was verified using quantitative polymerase chain reaction, which revealed that was downregulated in AAA, whereas , and were upregulated; there was no significant difference in PI3 expression. Our study shows that normal vascular and AAA samples can be distinguished via the infiltration of immune cells. Five genes, , and , may play important roles in the development, diagnosis, and treatment of AAA.
每年约有13000人死于腹主动脉瘤(AAA)。本研究旨在利用生物信息学方法鉴定在AAA中起重要作用的免疫反应相关基因。我们从基因表达综合数据库下载了与AAA相关的GSE57691和GSE98278数据集,其中包括80个AAA样本和10个正常血管样本。使用CIBERSORT分析样本并检测22种免疫细胞的浸润情况及其差异和相关性。主成分分析显示正常血管样本和AAA样本中免疫细胞浸润存在显著差异。在正常血管组织中发现高比例的CD4 T细胞、活化肥大细胞、静息自然杀伤细胞以及其他12种免疫细胞,而在AAA组织中发现高比例的巨噬细胞、CD8 T细胞、静息肥大细胞以及其他6种免疫细胞。在所选样本中,我们鉴定出39个上调基因(涉及生长因子活性、激素受体结合和细胞因子受体活性)和133个下调基因(涉及T细胞活化、细胞趋化性和免疫反应介质调节)。使用STRING数据库和Cytoscape软件筛选关键的差异表达免疫反应相关基因。通过构建蛋白质-蛋白质相互作用网络,鉴定出两个下调基因 和 ,以及三个上调基因 、 和 。对差异表达基因进行功能富集分析,并使用定量聚合酶链反应验证AAA样本中五个关键基因的表达,结果显示 在AAA中下调,而 、 和 上调;PI3表达无显著差异。我们的研究表明,正常血管样本和AAA样本可通过免疫细胞浸润来区分。 、 和 这五个基因可能在AAA的发生、诊断和治疗中起重要作用。