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基于基因表达谱鉴定与人类腹主动脉瘤相关的关键基因

Identification of key genes associated with the human abdominal aortic aneurysm based on the gene expression profile.

作者信息

Chen Xudong, Zheng Chengfei, He Yunjun, Tian Lu, Li Jianhui, Li Donglin, Jin Wei, Li Ming, Zheng Shusen

机构信息

Department of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.

Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.

出版信息

Mol Med Rep. 2015 Dec;12(6):7891-8. doi: 10.3892/mmr.2015.4448. Epub 2015 Oct 15.

Abstract

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.

摘要

本研究旨在筛选与颈部腹主动脉瘤(AAA)相关的关键基因,并探讨AAA发生发展的分子机制。从基因表达综合数据库下载了基因表达谱GSE47472,其中包括14个AAA颈部样本和8个供体对照。将所有AAA样本分为两种类型以避免偏差。在AAA患者中筛选差异表达基因(DEG),随后使用微阵列数据线性模型或R语言中的Limma软件包与供体对照进行比较,接着进行基因本体富集分析。此外,基于DEG构建蛋白质 - 蛋白质相互作用(PPI)网络,使用Cytoscape插件检测高度连接区域。总共在AAA样本中鉴定出388个DEG。这些DEG主要与肢体发育相关,包括胚胎肢体发育和附属器发育。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AAA相关的四个转录因子。此外,HNF4A与其他三个转录因子间接相互作用。另外,从PPI网络中选择了六个簇。DEG筛选过程和相互作用网络的构建有助于深入了解AAA的机制。HNF4A可能通过与其他三个转录因子(E2F4、NCOR1和H4)相互作用在AAA发展中发挥重要作用,并且这种转录因子在AAA中的协同调控机制可能为治疗干预策略的开发提供合适的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e8/4758287/ff7b470b67ae/MMR-12-06-7891-g00.jpg

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