West China School of Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Department of Burn and Plastic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
BMC Cardiovasc Disord. 2021 Jan 6;21(1):14. doi: 10.1186/s12872-020-01838-x.
Aneurysm is a severe and fatal disease. This study aims to comprehensively identify the highly conservative co-expression modules and hub genes in the abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA) and intracranial aneurysm (ICA) and facilitate the discovery of pathogenesis for aneurysm.
GSE57691, GSE122897, and GSE5180 microarray datasets were downloaded from the Gene Expression Omnibus database. We selected highly conservative modules using weighted gene co‑expression network analysis before performing the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway and Reactome enrichment analysis. The protein-protein interaction (PPI) network and the miRNA-hub genes network were constructed. Furtherly, we validated the preservation of hub genes in three other datasets.
Two modules with 193 genes and 159 genes were identified as well preserved in AAA, TAA, and ICA. The enrichment analysis identified that these genes were involved in several biological processes such as positive regulation of cytosolic calcium ion concentration, hemostasis, and regulation of secretion by cells. Ten highly connected PPI networks were constructed, and 55 hub genes were identified. In the miRNA-hub genes network, CCR7 was the most connected gene, followed by TNF and CXCR4. The most connected miRNAs were hsa-mir-26b-5p and hsa-mir-335-5p. The hub gene module was proved to be preserved in all three datasets.
Our study highlighted and validated two highly conservative co-expression modules and miRNA-hub genes network in three kinds of aneurysms, which may promote understanding of the aneurysm and provide potential therapeutic targets and biomarkers of aneurysm.
动脉瘤是一种严重且致命的疾病。本研究旨在全面鉴定腹主动脉瘤（AAA）、胸主动脉瘤（TAA）和颅内动脉瘤（ICA）中的高度保守共表达模块和枢纽基因，以促进对动脉瘤发病机制的发现。
从基因表达综合数据库中下载 GSE57691、GSE122897 和 GSE5180 微阵列数据集。我们使用加权基因共表达网络分析选择高度保守的模块，然后进行基因本体论、京都基因与基因组百科全书通路和反应网络分析的富集分析。构建蛋白质-蛋白质相互作用（PPI）网络和 miRNA-枢纽基因网络。进一步，我们验证了三个其他数据集的枢纽基因的保存情况。
鉴定出两个包含 193 个基因和 159 个基因的模块在 AAA、TAA 和 ICA 中保存完好。富集分析表明，这些基因参与了几个生物学过程，如细胞质钙离子浓度的正调控、止血和细胞分泌的调节。构建了 10 个高度连接的 PPI 网络，鉴定出 55 个枢纽基因。在 miRNA-枢纽基因网络中，CCR7 是最连接的基因，其次是 TNF 和 CXCR4。最连接的 miRNA 是 hsa-mir-26b-5p 和 hsa-mir-335-5p。枢纽基因模块在所有三个数据集都被证明是保存的。
我们的研究强调并验证了三种动脉瘤中两个高度保守的共表达模块和 miRNA-枢纽基因网络，这可能有助于对动脉瘤的理解，并为动脉瘤提供潜在的治疗靶点和生物标志物。
