分析慢性血栓形成特征基因及与慢性血栓栓塞性肺动脉高压相关通路。
Analysis of genes characterizing chronic thrombosis and associated pathways in chronic thromboembolic pulmonary hypertension.
机构信息
Bengbu Medical College, Bengbu, China.
Xuzhou Central Hospital, Xuzhou, China.
出版信息
PLoS One. 2024 Mar 7;19(3):e0299912. doi: 10.1371/journal.pone.0299912. eCollection 2024.
PURPOSE
In chronic thromboembolic pulmonary hypertension (CTEPH), fibrosis of thrombi in the lumen of blood vessels and obstruction of blood vessels are important factors in the progression of the disease. Therefore, it is important to explore the key genes that lead to chronic thrombosis in order to understand the development of CTEPH, and at the same time, it is beneficial to provide new directions for early identification, disease prevention, clinical diagnosis and treatment, and development of novel therapeutic agents.
METHODS
The GSE130391 dataset was downloaded from the Gene Expression Omnibus (GEO) public database, which includes the full gene expression profiles of patients with CTEPH and Idiopathic Pulmonary Arterial Hypertension (IPAH). Differentially Expressed Genes (DEGs) of CTEPH and IPAH were screened, and then Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analyses were performed on the DEGs; Weighted Gene Co-Expression Network Analysis (WGCNA) to screen the key gene modules and take the intersection genes of DEGs and the key module genes in WGCNA; STRING database was used to construct the protein-protein interaction (PPI) network; and cytoHubba analysis was performed to identify the hub genes.
RESULTS
A total of 924 DEGs were screened, and the MEturquoise module with the strongest correlation was selected to take the intersection with DEGs A total of 757 intersecting genes were screened. The top ten hub genes were analyzed by cytoHubba: IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4.
CONCLUSION
IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4 have diagnostic and therapeutic value in CTEPH disease, especially playing a role in chronic thrombosis. The discovery of NF-κB, AP-1 transcription factors, and TNF signaling pathway through pivotal genes may be involved in the disease progression process.
目的
在慢性血栓栓塞性肺动脉高压（CTEPH）中，血管腔中血栓的纤维化和血管阻塞是疾病进展的重要因素。因此，探索导致慢性血栓形成的关键基因对于了解 CTEPH 的发展具有重要意义，同时也有利于为早期识别、疾病预防、临床诊断和治疗以及新型治疗药物的开发提供新的方向。
方法
从基因表达综合数据库（GEO）公共数据库中下载 GSE130391 数据集，该数据集包含 CTEPH 和特发性肺动脉高压（IPAH）患者的全基因表达谱。筛选 CTEPH 和 IPAH 的差异表达基因（DEGs），然后对 DEGs 进行京都基因与基因组百科全书（KEGG）和基因本体论（GO）功能富集分析；采用加权基因共表达网络分析（WGCNA）筛选关键基因模块，并取 DEGs 与 WGCNA 中关键模块基因的交集；使用 STRING 数据库构建蛋白质-蛋白质相互作用（PPI）网络；通过 cytoHubba 分析鉴定枢纽基因。
结果
共筛选出 924 个 DEGs，选择相关性最强的 MEturquoise 模块与 DEGs 取交集，共筛选出 757 个交集基因。通过 cytoHubba 分析，选取前 10 个枢纽基因：IL-1B、CXCL8、CCL22、CCL5、CCL20、TNF、IL-12B、JUN、EP300 和 CCL4。
结论
IL-1B、CXCL8、CCL22、CCL5、CCL20、TNF、IL-12B、JUN、EP300 和 CCL4 在 CTEPH 疾病中具有诊断和治疗价值，尤其是在慢性血栓形成中起作用。通过关键基因发现 NF-κB、AP-1 转录因子和 TNF 信号通路可能参与疾病进展过程。
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