Identification of potential key pathways, genes and circulating markers in the development of intracranial aneurysm based on weighted gene co-expression network analysis

Identification of potential key pathways, genes and circulating markers in the development of intracranial aneurysm based on weighted gene co-expression network analysis
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基于加权基因共表达网络分析识别颅内动脉瘤发生过程中的潜在关键通路、基因和循环标志物

DOI:
10.1080/21691401.2020.1770264
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发表时间:
2020-01-01
影响因子:
5.8
通讯作者:
Duysenbi, Serick
Duysenbi, Serick
中科院分区:
工程技术2区
文献类型:
--
作者:
Du, Guojia;Geng, Dangmurenjiafu;Duysenbi, Serick

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摘要背景颅内动脉瘤(IA)是一种脑控制薄弱所致的疾病,以脑动脉局部扩张或扩张为特征。本研究旨在通过加权基因相关网络分析(WGCNA)构建基因共表达网络,以探索IA发生发展的潜在关键途径和基因。方法从基因表达总表(GEO)数据库下载6个IA相关基因表达数据集,用于鉴定差异表达基因(DEG)。WGCNA用于识别与IA相关的模块。通过功能富集化分析,探索其潜在的生物学功能。用ROC分析寻找预测IA的标志物。结果紫色、绿黄色和黄色模组与未破裂的颅内动脉瘤显著相关,而蓝色和绿松石模组与破裂的颅内动脉瘤显著相关。与IA显著相关的功能模块丰富于核糖体、谷胱甘肽代谢、cAMP信号通路、溶酶体、糖胺多糖降解等途径。CD163、FCEREG、FPR1、ITGAM、NLRC4、PDG和TYROBP是颅内破裂动脉瘤和血清中表达上调的基因,这些基因是预测IA破裂的潜在循环标志物。结论通过WGCNA分析,找出了与IA相关的潜在关键通路、基因和循环标志物,可预测IA破裂。
Abstract Background Intracranial aneurysm (IA) is a disease resulted from weak brain control, characterized by local expansion or dilation of brain artery. This study aimed to construct a gene co-expression network by Weighted Gene Correlation Network Analysis (WGCNA) to explore the potential key pathways and genes for the development of IA. Method Six IA-related gene expression data sets were downloaded from the Gene Expression Omnibus (GEO) database for identifying differentially expressed genes (DEGs). WGCNA was used to identify modules associated with IA. Functional enrichment analysis was used to explore the potential biological functions. ROC analysis was used to find markers for predicting IA. Results Purple, greenyellow and yellow modules were significantly associated with unruptured intracranial aneurysms, while blue and turquoise modules were significantly associated with ruptured intracranial aneurysms. Functional modules significantly related to IA were enriched in Ribosome, Glutathione metabolism, cAMP signalling pathway, Lysosome, Glycosaminoglycan degradation and other pathways. CD163, FCEREG, FPR1, ITGAM, NLRC4, PDG, and TYROBP were up-regulated ruptured intracranial aneurysms and serum, these genes were potential circulating markers for predicting IA rupture. Conclusions Potential IA-related key pathways, genes and circulating markers were identified for predicting IA rupture by WGCNA analysis.