Identification of driver genes associated with chemotherapy resistance of Ewing's sarcoma.
Identification of driver genes associated with chemotherapy resistance of Ewing's sarcoma.
复制标题
鉴定与尤文氏肉瘤化疗耐药相关的驱动基因。
DOI：
10.2147/ott.s172190
复制
发表时间：
2018
影响因子：
4
通讯作者：
Huang G
中科院分区：
文献类型：
--
作者：
Liao H;Xie X;Xu Y;Huang G
本研究的目的是鉴定与尤文肉瘤化疗耐药相关的驱动基因和尤文肉瘤治疗的潜在靶点。两个mRNA微阵列数据集，GSE 12102和GSE 17679，从基因表达综合数据库中下载，其中包含94个人类尤文肉瘤样本，包括65个来自经历复发的患者和29个来自没有疾病证据的患者。用LIMMA软件包R鉴定表达基因（DEG）。随后，使用用于注释、可视化和集成分析的数据库对DEG进行基因本体和京都基因百科全书和基因组途径富集分析。使用Cytoscape软件构建蛋白质-蛋白质相互作用网络，并使用分子复合物检测进行模块分析。共鉴定了206个上调的DEG和141个下调的DEG。上调的DEG主要富集在DNA复制、核质和蛋白激酶结合中，分别用于生物过程、细胞组分和分子功能。下调的DEG主要参与受体聚集、膜筏和配体依赖性核受体结合。DEG的蛋白质相互作用网络由150个节点和304个相互作用组成。鉴定了13个枢纽基因，生物学分析显示这些基因主要在细胞分裂、细胞周期和有丝分裂中富集。此外，基于接近中心性、介数中心性和程度中心性，将三个最显著的基因鉴定为GAPDH、AURKA和EHMT 2。显著网络模块由9个基因组成。这些基因主要富集在有丝分裂的核分裂，有丝分裂的染色体凝聚，和核质。这些枢纽基因，尤其是GAPDH、AURKA和EHMT 2，可能与尤文肉瘤化疗耐药的进展密切相关，需要进一步的实验来证实。
The aim of this study was to identify the driver genes associated with chemotherapy resistance of Ewing’s sarcoma and potential targets for Ewing’s sarcoma treatment. Two mRNA microarray datasets, GSE12102 and GSE17679, were downloaded from the Gene Expression Omnibus database, which contain 94 human Ewing’s sarcoma samples, including 65 from those who experienced a relapse and 29 from those with no evidence of disease. The differen tially expressed genes (DEGs) were identified using LIMMA package R. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for DEGs using Database for Annotation, Visualization and Integrated Analysis. The protein–protein interaction network was constructed using Cytoscape software, and module analysis was performed using Molecular Complex Detection. A total of 206 upregulated DEGs and 141 downregulated DEGs were identified. Upregulated DEGs were primarily enriched in DNA replication, nucleoplasm and protein kinase binding for biological processes, cellular component and molecular functions, respectively. Downregulated DEGs were predominantly involved in receptor clustering, membrane raft, and ligand-dependent nuclear receptor binding. The protein–protein interaction network of DEGs consisted of 150 nodes and 304 interactions. Thirteen hub genes were identified, and biological analysis revealed that these genes were primarily enriched in cell division, cell cycle, and mitosis. Furthermore, based on closeness centrality, betweenness centrality, and degree centrality, the three most significant genes were identified as GAPDH, AURKA, and EHMT2. Furthermore, the significant network module was composed of nine genes. These genes were primarily enriched in mitotic nuclear division, mitotic chromosome condensation, and nucleoplasm. These hub genes, especially GAPDH, AURKA, and EHMT2, may be closely associated with the progression of Ewing’s sarcoma chemotherapy resistance, and further experiments are needed for confirmation.