Identification of biomarkers and analysis of infiltrated immune cells in stable and ruptured abdominal aortic aneurysms.

Identification of biomarkers and analysis of infiltrated immune cells in stable and ruptured abdominal aortic aneurysms.
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稳定和破裂腹主动脉瘤中生物标志物的鉴定和浸润免疫细胞的分析

DOI:
10.3389/fcvm.2022.941185
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发表时间:
2022
影响因子:
3.6
通讯作者:
Luo, Fanyan
Luo, Fanyan
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Yubin;Ouyang, Tianyu;Fang, Cheng;Tang, Can-e;Lei, Kaibo;Jiang, Longtan;Luo, Fanyan

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腹主动脉瘤(AAA)的死亡率在老年人群中非常高。本研究旨在确定AAA和主动脉破裂的潜在生物标志物,并分析AAA稳定和破裂标本中免疫细胞的渗透情况。下载了GSE47472、GSE57691和GSE98278的原始数据。经数据处理后,构建了共表达基因网络。使用注释、可视化和综合发现数据库进行AAA和主动脉破裂相关基因模块的基因本体论和途径丰富分析。采用基因集浓缩分析(GSEA)和基因集变异分析(GSVA)进行进一步的浓缩分析。CiberSort工具用于分析样本中免疫细胞的相对丰度。分析不同样本间差异表达的免疫相关基因。通过极端梯度增强构建预测模型,并根据特征重要性识别HUB基因。蓝色和黄色模块与AAA显著相关,这些模块中的基因分别与主动脉壁和免疫反应相关。在主动脉破裂方面,最相关的模块在炎症反应中显著丰富。GSEA和GSVA结果提示免疫细胞和炎症反应参与了AAA和主动脉破裂的发生发展。不同样品间免疫细胞的渗透和免疫相关基因的表达水平存在显著差异。NFKB1可能是AAA和主动脉破裂炎症反应的重要转录因子。在构建预测模型后,CD19、SEL和CCR7被选为AAA的中心基因,而OAS3、IFIT1和IFI44L被确定为主动脉破裂的中心基因。腹主动脉壁变薄和免疫反应均参与了AAA的发生,而炎症反应与主动脉破裂密切相关。不同样品间免疫细胞的渗入有显著差异。NFKB1可能是AAA和主动脉破裂的重要转录因子。CD19、Sell和CCR7对AAA有潜在的诊断价值。OAS3、IFIT1和IFI44L可能是主动脉破裂的预测因子。
The mortality rate of abdominal aortic aneurysm (AAA) is extremely high in the older population. This study aimed to identify potential biomarkers of AAA and aortic rupture and analyze infiltration of immune cells in stable and ruptured AAA samples. Raw data of GSE47472, GSE57691, and GSE98278 were downloaded. After data processing, the co-expression gene networks were constructed. Gene Ontology and pathway enrichment analysis of AAA- and aortic rupture-related gene modules were conducted using the Database for Annotation, Visualization, and Integrated Discovery. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used for further enrichment analysis. The CIBERSORT tool was used to analyze the relative abundance of immune cells in samples. Differentially expressed immune-related genes were analyzed between different samples. Predictive models were constructed via extreme gradient boosting, and hub genes were identified according to feature importance. Blue and yellow modules were significantly related to AAA, and genes in these modules were associated with the aortic wall and immune response, respectively. In terms of aortic rupture, the most relevant module was significantly enriched in the inflammatory response. The results of GSEA and GSVA suggested that immune cells and the inflammatory response were involved in the development of AAA and aortic rupture. There were significant differences in the infiltration of immune cells and expression levels of immune-related genes among different samples. NFKB1 might be an important transcription factor mediating the inflammatory response of AAA and aortic rupture. After the construction of a predictive model, CD19, SELL, and CCR7 were selected as hub genes for AAA whereas OAS3, IFIT1, and IFI44L were identified as hub genes for aortic rupture. Weakening of the aortic wall and the immune response both contributed to the development of AAA, and the inflammatory response was closely associated with aortic rupture. The infiltration of immune cells was significantly different between different samples. NFKB1 might be an important transcription factor in AAA and aortic rupture. CD19, SELL, and CCR7 had potential diagnostic value for AAA. OAS3, IFIT1, and IFI44L might be predictive factors for aortic rupture.
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影响因子: 3.6
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