Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Ziqiang Street 218, Changchun, Jilin 130041, China.
Biomed Res Int. 2019 Jul 14;2019:3629751. doi: 10.1155/2019/3629751. eCollection 2019.
Thoracic aortic dissection (TAD) is a catastrophic disease worldwide, but the pathogenic genes and pathways are largely unclear. This study aims at integrating two gene expression profile datasets and verifying hub genes and pathways involved in TAD as well as exploring potential molecular mechanisms. We will combine our mRNAs expression profile (6 TAD tissues versus 6 non-TAD tissues) and GSE52093 downloaded from the Gene Expression Omnibus (GEO) database. The two mRNAs expression profiles contained 13 TAD aortic tissues and 11 non-TAD tissues. The two expression profile datasets were integrated and we found out coexpression of differentially expressed genes (DEGs) using bioinformatics methods. The gene ontology and pathway enrichment of DEGs were performed by DAVID and Kyoto Encyclopedia of Genes and Genomes online analyses, respectively. The protein-protein interaction networks of the DEGs were constructed according to the data from the STRING database. Cytohubber calculating result shows the top 10 hub genes with CDC20, AURKA, RFC4, MCM4, TYMS, MCM2, DLGAP5, FANCI, BIRC5, and POLE2. Module analysis revealed that TAD was associated with significant pathways including cell cycle, vascular smooth muscle contraction, and adrenergic signaling in cardiomyocytes. The qRT-PCR result showed that the expression levels of all the hub genes were significantly increased in OA samples (p < 0.05), and these candidate genes could be used as potential diagnostic biomarkers and therapeutic targets of TAD.
胸主动脉夹层(TAD)是一种全球性的灾难性疾病,但致病基因和途径在很大程度上尚不清楚。本研究旨在整合两个基因表达谱数据集,并验证 TAD 涉及的关键基因和途径,以及探索潜在的分子机制。我们将结合我们的 mRNA 表达谱(6 个 TAD 组织与 6 个非 TAD 组织)和从基因表达综合数据库(GEO)下载的 GSE52093。这两个 mRNA 表达谱包含 13 个 TAD 主动脉组织和 11 个非 TAD 组织。我们整合了这两个表达谱数据集,并使用生物信息学方法发现差异表达基因(DEGs)的共表达。通过 DAVID 和京都基因与基因组百科全书在线分析,分别对 DEGs 的基因本体和通路富集进行了分析。根据 STRING 数据库的数据,构建了 DEGs 的蛋白质-蛋白质相互作用网络。Cytohubber 计算结果显示,CDC20、AURKA、RFC4、MCM4、TYMS、MCM2、DLGAP5、FANCI、BIRC5 和 POLE2 是前 10 个具有 hub 特性的基因。模块分析显示,TAD 与包括细胞周期、血管平滑肌收缩和心肌细胞肾上腺素能信号在内的显著途径有关。qRT-PCR 结果显示,所有 hub 基因在 OA 样本中的表达水平均显著升高(p<0.05),这些候选基因可以作为 TAD 的潜在诊断生物标志物和治疗靶点。