Deng Yajun, Xie Qiqi, Zhang Guangzhi, Li Shaoping, Wu Zuolong, Ma Zhanjun, He Xuegang, Gao Yicheng, Wang Yonggang, Kang Xuewen, Wang Jing
Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China.
Key Laboratory of Orthopedic Disease of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China.
Oncol Lett. 2019 Dec;18(6):6431-6442. doi: 10.3892/ol.2019.11044. Epub 2019 Nov 4.
Ewing's sarcoma (ES) is a common malignant bone tumor in children and adolescents. Although great efforts have been made to understand the pathogenesis and development of ES, the underlying molecular mechanism remains unclear. The present study aimed to identify new key genes as potential biomarkers for the diagnosis, targeted therapy or prognosis of ES. mRNA expression profile chip data sets GSE17674, GSE17679 and GSE45544 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the R software limma package, and functional and pathway enrichment analyses were performed using the enrichplot package and GSEA software. The NetworkAnalyst online tool, as well as Cytoscape and its plug-ins cytoHubba and NetworkAnalyzer, were used to construct a protein-protein interaction network (PPI) and conduct module analysis to screen key (hub) genes. LABSO COX regression and overall survival (OS) analysis of the Hub genes were performed. A total of 211 DEGs were obtained by integrating and analyzing the three data sets. The functions and pathways of the DEGs were mainly associated with the regulation of small-molecule metabolic processes, cofactor-binding, amino acid, proteasome and ribosome biosynthesis in eukaryotes, as well as the Rac1, cell cycle and P53 signaling pathways. A total of one important module and 20 hub genes were screened from the PPI network using the Maximum Correlation Criteria algorithm of cytoHubba. LASSO COX regression results revealed that titin (), fast skeletal muscle troponin T, skeletal muscle actin α-actin, nebulin, troponin C type 2 (fast), myosin light-chain 3 (), slow skeletal muscle troponin T (), myosin-binding protein C1 slow-type, tropomyosin 3 and myosin heavy-chain 7 were associated with prognosis in patients with ES. The Kaplan-Meier curves demonstrated that high mRNA expression levels of (P<0.001), (P=0.049), titin-cap (P=0.04), tropomodulin 1 (P=0.011), troponin I2 fast skeletal type (P=0.021) and (P=0.017) were associated with poor OS in patients with ES. In conclusion, the DEGs identified in the present study may be key genes in the pathogenesis of ES, three of which, namely and , may be potential prognostic biomarkers for ES.
尤因肉瘤（ES）是儿童和青少年常见的恶性骨肿瘤。尽管在了解ES的发病机制和发展方面已做出了巨大努力，但其潜在的分子机制仍不清楚。本研究旨在鉴定新的关键基因，作为ES诊断、靶向治疗或预后的潜在生物标志物。从基因表达综合数据库下载了mRNA表达谱芯片数据集GSE17674、GSE17679和GSE45544。使用R软件的limma包筛选差异表达基因（DEG），并使用enrichplot包和GSEA软件进行功能和通路富集分析。使用NetworkAnalyst在线工具以及Cytoscape及其插件cytoHubba和NetworkAnalyzer构建蛋白质-蛋白质相互作用网络（PPI）并进行模块分析，以筛选关键（枢纽）基因。对枢纽基因进行LABSO COX回归和总生存期（OS）分析。通过整合和分析这三个数据集，共获得211个DEG。DEG的功能和通路主要与小分子代谢过程的调节、辅因子结合、氨基酸、蛋白酶体和真核生物中的核糖体生物合成，以及Rac1、细胞周期和P53信号通路有关。使用cytoHubba的最大相关标准算法从PPI网络中筛选出1个重要模块和20个枢纽基因。LASSO COX回归结果显示，肌联蛋白（）、快骨骼肌肌钙蛋白T、骨骼肌肌动蛋白α-肌动蛋白、伴肌动蛋白、2型（快）肌钙蛋白C、肌球蛋白轻链3（）、慢骨骼肌肌钙蛋白T（）、慢型肌球蛋白结合蛋白C1、原肌球蛋白3和肌球蛋白重链7与ES患者的预后相关。Kaplan-Meier曲线表明，（P<0.001）、（P=0.049）、肌联蛋白帽（P=0.04）、原肌球蛋白调节蛋白1（P=0.011）、快骨骼肌型肌钙蛋白I2（P=0.021）和（P=0.017）的高mRNA表达水平与ES患者的不良OS相关。总之，本研究中鉴定的DEG可能是ES发病机制中的关键基因，其中三个基因，即和，可能是ES的潜在预后生物标志物。
