Zhou Shiyong, Liu Pengfei, Jiang Wenhua, Zhang Huilai
Department of Lymphoma, Sino-US Center of Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China.
Department of Radiotherapy, Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
Oncol Lett. 2017 Jun;13(6):4267-4275. doi: 10.3892/ol.2017.5968. Epub 2017 Mar 31.
The purpose of the present study was to explore the effect of propranolol on angiosarcoma, and the potential target genes involved in the processes of proliferation and differentiation of angiosarcoma tumor cells. The mRNA expression profile (GSE42534) was downloaded from the Gene Expressed Omnibus database, including three samples without propranolol treatment (control), three samples with propranolol treatment for 4 h and three samples with propranolol treatment for 24 h. The differentially expressed genes (DEGs) in angiosarcoma tumor cells with or without propranolol treatment were obtained via the limma package of R and designated DEGs-4 h and DEGs-24 h. The DEGs-24 h group was divided into two sets. Set 1 contained the DEGs also contained in the DEGs-4 h group. Set 2 contained the remainder of the DEGs. Functional and pathway enrichment analysis of sets 1 and 2 was performed. The protein-protein interaction (PPI) networks of sets 1 and 2 were constructed, termed PPI 1 and PPI 2, and visualized using Cytoscape software. Modules of the two PPI networks were analyzed, and their topological structures were simulated using the tYNA platform. A total of 543 and 2,025 DEGs were identified in angiosarcoma tumor cells treated with propranolol for 4 and 24 h, respectively, compared with the control group. A total of 401 DEGs were involved in DEGs-4 h and DEGs-24 h, including metallothionein 1, heme oxygenase 1, WW domain-binding protein 2 and sequestosome 1. Certain significantly enriched gene ontology (GO) terms and pathways of sets 1 and 2 were identified, containing 28 overlapping GO terms. Furthermore, 121 nodes and 700 associated pairs were involved in PPI 1, whereas 1,324 nodes and 11,839 associated pairs were involved in PPI 2. A total of 45 and 593 potential target genes were obtained according to the node degrees of PPI 1 and PPI 2. The results of the present study indicated that a number of potential target genes, including AXL receptor tyrosine kinase, coatomer subunit α, DR1-associated protein 1 and ERBB receptor feedback inhibitor 1 may be involved in the effect of propranolol on angiosarcoma.
本研究的目的是探讨普萘洛尔对血管肉瘤的影响,以及参与血管肉瘤肿瘤细胞增殖和分化过程的潜在靶基因。从基因表达综合数据库下载了mRNA表达谱(GSE42534),包括三个未经普萘洛尔处理的样本(对照)、三个经普萘洛尔处理4小时的样本和三个经普萘洛尔处理24小时的样本。通过R语言的limma软件包获得普萘洛尔处理组和未处理组血管肉瘤肿瘤细胞中的差异表达基因(DEGs),分别命名为DEGs - 4h和DEGs - 24h。将DEGs - 24h组分为两组。第1组包含也存在于DEGs - 4h组中的DEGs。第2组包含其余的DEGs。对第1组和第2组进行功能和通路富集分析。构建第1组和第2组的蛋白质 - 蛋白质相互作用(PPI)网络,分别称为PPI 1和PPI 2,并使用Cytoscape软件进行可视化。分析两个PPI网络的模块,并使用tYNA平台模拟其拓扑结构。与对照组相比,在普萘洛尔处理4小时和24小时的血管肉瘤肿瘤细胞中分别鉴定出543个和2,025个DEGs。共有401个DEGs同时存在于DEGs - 4h和DEGs - 24h中,包括金属硫蛋白1、血红素加氧酶1、WW结构域结合蛋白2和聚集体蛋白1。确定了第1组和第2组某些显著富集的基因本体(GO)术语和通路,包含28个重叠的GO术语。此外,PPI 1包含121个节点和700个相关对,而PPI 2包含1,324个节点和11,839个相关对。根据PPI 1和PPI 2的节点度分别获得45个和593个潜在靶基因。本研究结果表明,一些潜在靶基因,包括AXL受体酪氨酸激酶、外被体亚基α、DR1相关蛋白1和ERBB受体反馈抑制剂1,可能参与普萘洛尔对血管肉瘤的作用。