Jiang Wenhua, Liu Pengfei, Li Xiaodong, Wang Ping
Department of Radiotherapy, 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, Sino-US Center of Lymphoma and Leukemia, Tianjin 300060, P.R. China.
Department of Radiotherapy, Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
Oncol Lett. 2017 Apr;13(4):2623-2630. doi: 10.3892/ol.2017.5779. Epub 2017 Feb 24.
The aim of the present study was to identify the target genes of cediranib and the associated signaling pathways in alveolar soft part sarcoma (ASPS). A microarray dataset (GSE32569) was obtained from the Gene Expression Omnibus database. The R software package was used for data normalization and screening of differentially expressed genes (DEGs). The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology analysis. Gene Set Enrichment Analysis was performed to obtain the up- and downregulated pathways in ASPS. The Distant Regulatory Elements of co-regulated genes database was used to identify the transcription factors (TFs) that were enriched in the signaling pathways. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database and was visualized using Cytoscape software. A total of 71 DEGs, including 59 upregulated genes and 12 downregulated genes, were identified. Gene sets associated with ASPS were enriched primarily in four signaling pathways: The phenylalanine metabolism pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, the taste transduction pathway and the intestinal immune network for the production of immunoglobulin A. Furthermore, 107 TFs were identified to be enriched in the MAPK signaling pathway. Certain genes, including those coding for Fms-like tyrosine kinase 1, kinase insert domain receptor, E-selectin and platelet-derived growth factor receptor D, that were associated with other genes in the PPI network, were identified. The present study identified certain potential target genes and the associated signaling pathways of cediranib action in ASPS, which may be helpful in understanding the efficacy of cediranib and the development of new targets for cediranib.
本研究的目的是确定西地尼布在肺泡软组织肉瘤（ASPS）中的靶基因及相关信号通路。从基因表达综合数据库中获取了一个微阵列数据集（GSE32569）。使用R软件包进行数据标准化和差异表达基因（DEG）筛选。利用注释、可视化和综合发现数据库进行基因本体分析。进行基因集富集分析以获得ASPS中上调和下调的通路。使用共调控基因的远距离调控元件数据库来识别在信号通路中富集的转录因子（TF）。使用检索相互作用基因/蛋白质的搜索工具数据库构建蛋白质-蛋白质相互作用（PPI）网络，并使用Cytoscape软件进行可视化。共鉴定出71个DEG，包括59个上调基因和12个下调基因。与ASPS相关的基因集主要富集于四个信号通路：苯丙氨酸代谢通路、丝裂原活化蛋白激酶（MAPK）信号通路、味觉转导通路和产生免疫球蛋白A的肠道免疫网络。此外，鉴定出107个TF在MAPK信号通路中富集。在PPI网络中，确定了某些与其他基因相关的基因，包括编码Fms样酪氨酸激酶1、激酶插入结构域受体、E选择素和血小板衍生生长因子受体D的基因。本研究确定了西地尼布在ASPS中的某些潜在靶基因及相关信号通路，这可能有助于理解西地尼布的疗效和开发西地尼布的新靶点。
