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Analysis of genes characterizing chronic thrombosis and associated pathways in chronic thromboembolic pulmonary
Shizhang Zhan1, Liu Wang2, Wenping Wang1
1Bengbu Medical College, Bengbu, China.
Insights
Researchers identified key genes like IL-1B and TNF involved in chronic thromboembolic pulmonary hypertension (CTEPH). These genes show potential for early diagnosis and novel treatments for CTEPH, a condition marked by blood vessel obstruction.
Area of Science:
- * Genomics and bioinformatics
- * Molecular biology
- * Pulmonary vascular disease research
Background:
- * Chronic thromboembolic pulmonary hypertension (CTEPH) involves thrombus fibrosis and vascular obstruction, critical for disease progression.
- * Understanding key genes in chronic thrombosis is vital for CTEPH development insights.
- * Identifying these genes aids early detection, prevention, and therapeutic strategies for CTEPH.
Purpose of the Study:
- * To identify key genes contributing to chronic thrombosis in CTEPH.
- * To explore potential diagnostic and therapeutic targets for CTEPH.
- * To elucidate molecular pathways involved in CTEPH pathogenesis.
Main Methods:
- * Analysis of Gene Expression Omnibus (GEO) dataset GSE130391 for CTEPH and Idiopathic Pulmonary Arterial Hypertension (IPAH) gene expression profiles.
- * Screening of Differentially Expressed Genes (DEGs) followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses.
- * Application of Weighted Gene Co-Expression Network Analysis (WGCNA), STRING database for protein-protein interaction (PPI) network construction, and cytoHubba for hub gene identification.
Main Results:
- * Identification of 924 DEGs between CTEPH and IPAH.
- * Selection of the MEturquoise module and screening of 757 intersecting genes.
- * Determination of ten hub genes: IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4.
Conclusions:
- * The identified hub genes (IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, CCL4) possess diagnostic and therapeutic potential for CTEPH.
- * These genes are implicated in the chronic thrombosis characteristic of CTEPH.
- * The NF-κB, AP-1 transcription factors, and TNF signaling pathways, highlighted by these pivotal genes, likely contribute to CTEPH progression.
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.
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