Bioinformatics-based study to detect chemical compounds that show potential as treatments for pulmonary thromboembolism

• Published in: International journal of molecular medicine 2019-01, Vol.43 (1), p.276-284
• Main Authors: Sun, Keyu, Xie, Zichen, Wang, Jiqin, Ling, Meirong, Li, Yanyan, Qiu, Chao
• Format: Article
• Language: English
• Subjects: Bioinformatics; Biosynthesis; Blood clots; Cardiomyocytes; Cardiomyopathy; Care and treatment; Datasets; Encyclopedias; Gene expression; Genomes; Hypoxia; Kinases; Ligands; Muscle contraction; Parasitic diseases; Proteins; Pulmonary arteries; Pulmonary embolism; Pulmonary hypertension; Thromboembolism; Tropical diseases; Tumor necrosis factor; Tumor necrosis factor-TNF; Veins & arteries
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2018.3987

The objectives of the present study comprised the recognition of major genes related to pulmonary thromboembolism (PTE) and the evaluation of their functional enrichment levels, in addition to the identification of small chemical molecules that may offer potential for use in PTE treatment. The RNA expression profiling of GSE84738 was obtained from the Gene Expression Omnibus database. Following data preprocessing, the differently expressed genes (DEGs) between the PTE group and the control group were identified using the Linear Models for Microarray package. Subsequently, the protein-protein interaction (PPI) network of these DEGs was examined using the Search Tool for the Retrieval of Interacting Genes/Proteins database, visualized via Cytoscape. The most significantly clustered modules in the network were identified using Multi Contrast Delayed Enhancement, a plugin of Cytoscape. Subsequently, functional enrichment analysis of the DEGs was performed, using the Database for Annotation Visualization and Integrated Discovery tool. Furthermore, the chemical-target interaction networks were investigated using the Comparative Toxicogenomics Database as visualized via Cytoscape. A total of 548 DEGs (262 upregulated and 286 downregulated) were identified in the PTE group, compared with the control group. The upregulated and downregulated genes were enriched in Gene Ontology terms related to inflammation and eye sarcolemma, respectively. Tumor necrosis factor (TNF) and erb-b2 receptor tyrosine kinase 2 (ERBB2) were upregulated genes that ranked higher in the PPI network (47 and 40 degrees, respectively) whereas C-JUN was the most downregulated gene (46). Small chemical molecules ethinyl (135), cyclosporin (126), thrombomodulin precursor (113) and tretinoin (111) had >100 degrees in the DEG-chemical interaction network. In addition, ethinyl targeted to TNF, whereas TNF and ERBB2 were targeted by cyclosporine, and tretinoin was a targeted chemical of ERBB2. Therefore, cyclosporine, ethinyl, and tretinoin may be potential targets for PTE treatment.