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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.

研究目的：在慢性血栓栓塞性肺动脉高压（chronic thromboembolic pulmonary hypertension, CTEPH）中，血管腔内血栓纤维化及血管阻塞是该病进展的重要因素。因此，探索介导慢性血栓形成的关键基因以阐明CTEPH的发生发展机制，可为该疾病的早期识别、疾病预防、临床诊疗及新型治疗药物研发提供全新方向。
研究方法：从基因表达综合（Gene Expression Omnibus, GEO）公共数据库下载GSE130391数据集，该数据集包含CTEPH患者与特发性肺动脉高压（Idiopathic Pulmonary Arterial Hypertension, IPAH）患者的全基因表达谱。筛选CTEPH与IPAH的差异表达基因（Differentially Expressed Genes, DEGs），随后对DEGs进行京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）及基因本体（Gene Ontology, GO）功能富集分析；通过加权基因共表达网络分析（Weighted Gene Co-Expression Network Analysis, WGCNA）筛选关键基因模块，并取DEGs与WGCNA关键模块基因的交集基因；借助STRING数据库构建蛋白质-蛋白质相互作用（protein-protein interaction, PPI）网络；运用cytoHubba分析识别核心基因（hub genes）。
研究结果：共筛选得到924个DEGs，选取相关性最强的MEturquoise模块与DEGs取交集，最终获得757个交集基因。通过cytoHubba分析得到排名前十的核心基因：IL-1B、CXCL8、CCL22、CCL5、CCL20、TNF、IL-12B、JUN、EP300及CCL4。
结论：IL-1B、CXCL8、CCL22、CCL5、CCL20、TNF、IL-12B、JUN、EP300及CCL4在CTEPH疾病中具有诊断与治疗价值，尤其在慢性血栓形成过程中发挥关键作用。通过核心基因发现NF-κB、AP-1转录因子及TNF信号通路可能参与该病的进展过程。