Zhang Kefeng, Gao Jianwen, Ni Yong
Department of Spinal Surgery, Shandong Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China.
Oncol Lett. 2017 Sep;14(3):2887-2893. doi: 10.3892/ol.2017.6519. Epub 2017 Jul 4.
The aim of the present study was to identify the key genes associated with osteosarcoma (OS) using a bioinformatics approach. Microarray data (GSE36004) was downloaded from the Gene Expression Omnibus database, including 19 OS cell lines and 6 normal controls. Differentially expressed genes (DEGs) in the OS cell lines were identified using the Limma package, and differentially methylated regions were screened with methyAnalysis in R. Copy number analysis was performed and genes with copy number gains/losses were further screened using DNAcopy and cghMCR packages. Functional enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery online tool, and protein-protein interactions were identified based on information obtained from the Search Tool for the Retrieval of Interacting Genes database. A total of 47 downregulated genes were screened in hyper-methylated regions, including the fragment crystallizable (Fc) region of immunoglobulin E, high affinity I, receptor for; γ polypeptide (), leptin () and feline Gardner-Rasheed sarcoma viral oncogene homolog (). In addition, a total of 17 upregulated genes, including the TPase family, AAA domain containing 2 () and cyclin-dependent kinase 4 (), exhibited copy number gains, while 5 downregulated genes, including Rho GTPase activating protein 9 () and major histocompatibility complex, class II, DO α (), exhibited copy number losses. These results indicate that hyper-methylation of , , and may serve a crucial function in the development of OS. In addition, copy number alterations of these DEGs, including , , and , may also contribute to OS progression. These DEGs may be candidate targets for the diagnosis and treatment of this disease.
本研究的目的是采用生物信息学方法鉴定与骨肉瘤(OS)相关的关键基因。从基因表达综合数据库下载了微阵列数据(GSE36004),包括19个OS细胞系和6个正常对照。使用Limma软件包鉴定OS细胞系中的差异表达基因(DEGs),并在R中使用甲基化分析筛选差异甲基化区域。进行拷贝数分析,并使用DNAcopy和cghMCR软件包进一步筛选具有拷贝数增加/减少的基因。使用在线注释、可视化和综合发现数据库工具进行功能富集分析,并根据从相互作用基因检索工具数据库获得的信息鉴定蛋白质-蛋白质相互作用。在高甲基化区域共筛选出47个下调基因,包括免疫球蛋白E的可结晶片段(Fc)区域、高亲和力I型受体γ多肽()、瘦素()和猫加德纳-拉希德肉瘤病毒癌基因同源物()。此外,共有17个上调基因,包括TPase家族、含AAA结构域的2()和细胞周期蛋白依赖性激酶4(),表现出拷贝数增加,而5个下调基因,包括Rho GTPase激活蛋白9()和主要组织相容性复合体II类DOα(),表现出拷贝数减少。这些结果表明,、和的高甲基化可能在OS的发生发展中起关键作用。此外,这些DEGs的拷贝数改变,包括、、和,也可能促进OS进展。这些DEGs可能是该疾病诊断和治疗的候选靶点。