Identification of potential causal genes and drug targets in pulmonary hypertension based on transcriptomic analysis...

Currently, there is no definitive treatment for pulmonary hypertension (PH). This study aims to utilize the GEO database and conduct Mendelian randomization (MR) analysis to identify new genetic targets for PH and investigate their potential pathogenic pathways and therapeutic drugs.

We identified key genes by combining the findings from MR and bioinformatics analyses of GEO datasets. We performed enrichment analysis to explore the functional roles of these key genes. Then, we constructed protein-protein interaction (PPI) and miRNA-mRNA networks to identify interacting proteins and miRNAs. Drug prediction analysis was conducted to propose potential therapeutic drugs. Finally, we validated the results through the GEO dataset, RT-PCR, and western blot experiments.

The joint analysis utilizing GEO databases and MR analysis identified two key genes, ITGA2B and TSPAN9 that exhibited significance across both analytical methods. The enrichment analysis indicated that the key genes were involved in critical biological functions and pathways, including cell adhesion, platelet activation, and the PI3K-Akt signaling pathway. The PPI and miRNA-mRNA networks further highlighted the significance of the key genes in PH. Drug prediction analysis revealed the potential of the key genes as therapeutic targets. The RT-PCR and western blot experiments validated the above findings.

By integrating bioinformatics and MR analysis, we found that ITGA2B and TSPAN9 have a causal relationship with PH. Our findings offer new insights into the molecular mechanism and potential treatment targets of PH, establishing a basis for future research and clinical applications.