Liao Hongyi, Xie Xianbiao, Xu Yuanyuan, Huang Gang
Department of Orthopedic Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, People's Republic of China.
Department of Orthopedic Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China,
Onco Targets Ther. 2018 Oct 15;11:6947-6956. doi: 10.2147/OTT.S172190. eCollection 2018.
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 , , and . 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 , , and , may be closely associated with the progression of Ewing's sarcoma chemotherapy resistance, and further experiments are needed for confirmation.
本研究旨在鉴定与尤因肉瘤化疗耐药相关的驱动基因以及尤因肉瘤治疗的潜在靶点。
从基因表达综合数据库下载了两个mRNA微阵列数据集GSE12102和GSE17679，其中包含94个人类尤因肉瘤样本，包括65例复发患者的样本和29例无疾病证据患者的样本。使用R语言的LIMMA软件包鉴定差异表达基因（DEG）。随后，使用注释、可视化和综合分析数据库对DEG进行基因本体论和京都基因与基因组百科全书通路富集分析。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。
共鉴定出206个上调的DEG和141个下调的DEG。上调的DEG分别主要富集于DNA复制、核质和蛋白质激酶结合，涉及生物学过程、细胞成分和分子功能。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-蛋白质相互作用网络由150个节点和304个相互作用组成。鉴定出13个枢纽基因，生物学分析表明这些基因主要富集于细胞分裂、细胞周期和有丝分裂。此外，基于紧密中心性、中介中心性和度中心性，确定了三个最显著的基因分别为 、 和 。此外，显著的网络模块由九个基因组成。这些基因主要富集于有丝分裂核分裂、有丝分裂染色体浓缩和核质。
这些枢纽基因，尤其是 、 和 ，可能与尤因肉瘤化疗耐药的进展密切相关，需要进一步实验进行证实。
