Emergency Department, Minhang Hospital, Fudan University, Shanghai 201100, P.R. China.
Institute of Biomedical Sciences, Fudan University, Shanghai 200032, P.R. China.
Int J Mol Med. 2019 Jan;43(1):276-284. doi: 10.3892/ijmm.2018.3987. Epub 2018 Nov 12.
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), cyclosporine (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.
本研究的目的包括识别与肺血栓栓塞症(PTE)相关的主要基因,并评估它们的功能富集水平,以及鉴定可能用于 PTE 治疗的小分子。从基因表达综合数据库中获得 GSE84738 的 RNA 表达谱。经过数据预处理,使用线性模型微阵列包识别 PTE 组和对照组之间的差异表达基因(DEGs)。随后,使用 Search Tool for the Retrieval of Interacting Genes/Proteins 数据库检查这些 DEGs 的蛋白质-蛋白质相互作用(PPI)网络,并通过 Cytoscape 可视化。使用 Cytoscape 的 Multi Contrast Delayed Enhancement 插件识别网络中最显著聚类的模块。随后,使用数据库注释可视化和综合发现工具对 DEGs 进行功能富集分析。此外,使用 Cytoscape 可视化的比较毒理学基因组数据库研究化学-靶标相互作用网络。与对照组相比,PTE 组中鉴定出 548 个 DEGs(262 个上调和 286 个下调)。上调和下调基因分别富集于与炎症和眼肌膜相关的基因本体论术语中。肿瘤坏死因子(TNF)和 erb-b2 受体酪氨酸激酶 2(ERBB2)是 PPI 网络中排名较高的上调基因(分别为 47 和 40 度),而 C-JUN 是下调程度最高的基因(46)。在 DEG-化学相互作用网络中,小分子乙炔基(135)、环孢素(126)、血栓调节蛋白前体(113)和维甲酸(111)的度数>100。此外,乙炔基靶向 TNF,而环孢素靶向 TNF 和 ERBB2,维甲酸是 ERBB2 的靶向化学物质。因此,环孢素、乙炔基和维甲酸可能是 PTE 治疗的潜在靶点。