Department of Neurosurgery, Jiangxi Provincial People's Hospital, Nanchang, 330006, Jiangxi, China.
Jiangxi University of Traditional Chinese Medicine, Nanchang, 330006, Jiangxi, China.
Sci Rep. 2022 Jan 7;12(1):225. doi: 10.1038/s41598-021-04390-6.
Intracranial aneurysm (IA) can cause fatal subarachnoid hemorrhage (SAH) after rupture, and identifying patients with unruptured IAs is essential for reducing SAH fatalities. The epithelial-mesenchymal transition (EMT) may be vital to IA progression. Here, identified key EMT-related genes in aneurysms and their pathogenic mechanisms via bioinformatic analysis. The GSE13353, GSE75436, and GSE54083 datasets from Gene Expression Omnibus were analyzed with limma to identify differentially expressed genes (DEGs) among unruptured aneurysms, ruptured aneurysms, and healthy samples. The results revealed that three EMT-related DEGs (ADIPOQ, WNT11, and CCL21) were shared among all groups. Coexpression modules and hub genes were identified via weighted gene co-expression network analysis, revealing two significant modules (red and green) and 14 EMT-related genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses suggested that cytokine interactions were closely related. Gene set enrichment analysis revealed that unruptured aneurysms were enriched for the terms "inflammatory response" and "vascular endothelial growth". Protein-protein interaction analysis identified seven key genes, which were evaluated with the GSE54083 dataset to determine their sensitivity and specificity. In the external validation set, we verified the differential expression of seven genes in unruptured aneurysms and normal samples. Together, these findings indicate that FN1, and SPARC may help distinguish normal patients from patients with asymptomatic IAs.
颅内动脉瘤 (IA) 破裂后可导致致命性蛛网膜下腔出血 (SAH)，因此识别未破裂的 IAs 对于降低 SAH 死亡率至关重要。上皮-间充质转化 (EMT) 可能对 IA 的进展至关重要。本研究通过生物信息学分析，确定了动脉瘤中与 EMT 相关的关键基因及其致病机制。从基因表达综合数据库中分析 GSE13353、GSE75436 和 GSE54083 数据集，使用 limma 识别未破裂动脉瘤、破裂动脉瘤和健康样本之间的差异表达基因 (DEGs)。结果表明，三个 EMT 相关的 DEGs（ADIPOQ、WNT11 和 CCL21）在所有组中均有表达。通过加权基因共表达网络分析鉴定了 coexpression 模块和枢纽基因，揭示了两个显著的模块（红色和绿色）和 14 个 EMT 相关基因。基因本体论和京都基因与基因组百科全书通路分析表明，细胞因子相互作用密切相关。基因集富集分析表明，未破裂的动脉瘤富含“炎症反应”和“血管内皮生长”等术语。蛋白质-蛋白质相互作用分析鉴定了七个关键基因，并在 GSE54083 数据集上进行了评估，以确定它们的敏感性和特异性。在外部验证集中，我们验证了七个基因在未破裂动脉瘤和正常样本中的差异表达。总之，这些发现表明 FN1 和 SPARC 可能有助于区分无症状 IA 患者和正常患者。
