Identification of key genes associated with the human abdominal aortic aneurysm based on the gene expression profile.
Identification of key genes associated with the human abdominal aortic aneurysm based on the gene expression profile.
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DOI：
10.3892/mmr.2015.4448
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发表时间：
2015-12
影响因子：
3.4
通讯作者：
Zheng S
中科院分区：
文献类型：
--
作者：
Chen X;Zheng C;He Y;Tian L;Li J;Li D;Jin W;Li M;Zheng S
本研究旨在筛选与颈部腹主动脉瘤(AAA)相关的关键基因，探讨AAA发生的分子机制。基因表达谱GSE47472，包括14个AAA颈部样本和8个供体对照，从基因表达总库下载。为避免偏差，将总的AAA样品分成两类。在AAA患者中筛选差异表达基因(DEG)，随后使用微阵列数据的线性模型或R中的LIMMA软件包与供者对照进行比较，然后进行基因本体浓缩分析。此外，基于DEGS构建了一个蛋白质-蛋白质相互作用(PPI)网络，以使用Cytoscape插件检测高度连通的区域。总共鉴定出AAA样本中的388个DEG。这些DEG主要与肢体发育有关，包括胚胎肢体发育和附肢发育。核受体共抑制因子1(NCOR1)、组蛋白4(H4)、E2F转录因子4(E2F4)和肝细胞核因子4α(HNF4a)是与腹主动脉瘤相关的4个转录因子。此外，HNF4a还与其他三个转录因子间接相互作用。此外，还从PPI网络中选择了六个分组。DEG筛选过程和相互作用网络的构建使人们能够了解AAA的机制。HNF4a可能通过与其他三种转录因子(E2F4、NCOR1和H4)的相互作用在AAA的发生发展中发挥重要作用，这种对AAA中转录因子的协调调节机制可能为AAA的治疗干预策略的发展提供一个合适的靶点。
The present study was aimed at screening the key genes associated with abdominal aortic aneurysm (AAA) in the neck, and to investigate the molecular mechanism underlying the development of AAA. The gene expression profile, GSE47472, including 14 AAA neck samples and eight donor controls, was downloaded from the Gene Expression Omnibus database. The total AAA samples were grouped into two types to avoid bias. Differentially expressed genes (DEGs) were screened in patients with AAA and subsequently compared with donor controls using linear models for microarray data, or the Limma package in R, followed by gene ontology enrichment analysis. Furthermore, a protein-protein interaction (PPI) network based on the DEGs was constructed to detect highly connected regions using a Cytoscape plugin. In total, 388 DEGs in the AAA samples were identified. These DEGs were predominantly associated with limb development, including embryonic limb development and appendage development. Nuclear receptor co-repressor 1 (NCOR1), histone 4 (H4), E2F transcription factor 4 (E2F4) and hepatocyte nuclear factor 4α (HNF4A) were the four transcription factors associated with AAA. Furthermore, HNF4A indirectly interacted with the other three transcription factors. Additionally, six clusters were selected from the PPI network. The DEG screening process and the construction of an interaction network enabled an understanding of the mechanism of AAA to be gleaned. HNF4A may exert an important role in AAA development through its interactions with the three other transcription factors (E2F4, NCOR1 and H4), and the mechanism of this coordinated regulation of the transcription factors in AAA may provide a suitable target for the development of therapeutic intervention strategies.