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基于微阵列基因表达谱的骨肉瘤基因功能分析

Gene function analysis in osteosarcoma based on microarray gene expression profiling.

作者信息

Zhao Liang, Zhang Jinghua, Tan Hongyu, Wang Weidong, Liu Yilin, Song Ruipeng, Wang Limin

机构信息

Department of Orthopedics, First Affiliated Hospital, Zhengzhou University Henan Province, China.

Department of Cardiology, The First Affiliated Hospital, Zhengzhou University Henan Province, China.

出版信息

Int J Clin Exp Med. 2015 Jul 15;8(7):10401-10. eCollection 2015.

Abstract

Osteosa rcoma is an aggressive malignant neoplasm that exhibits osteoblastic differentiation and produces malignant osteoid. The aim of this study was to find feature genes associated with osteosarcoma and correlative gene functions which can distinguish cancer tissues from non-tumor tissues. Gene expression profile GSE14359 was downloaded from Gene Expression Omnibus (GEO) database, including 10 osteosarcoma samples and 2 normal samples. The differentially expressed genes (DEGs) between osteosarcoma and normal specimens were identified using limma package of R. DAVID was applied to mine osteosarcoma associated genes and analyze the GO enrichment on gene functions and KEGG pathways. Then, corresponding protein-protein interaction (PPI) network of DEGs was constructed based on the data collected from STRING datasets. Principal component of top10 DEGs and PPI network of top 20 DEGs were further analyzed. Finally, transcription factors were predicted by uploading the two groups of DEGs to TfactS database. A total of 437 genes, including 114 up-regulated genes and 323 down-regulated genes, were filtered as DEGs, of which 46 were associated with osteosarcoma by Disease Module. GO and KEGG pathway enrichment analysis showed that genes mainly affected the process of immune response and the development of skeletal and vascular system. The PPI network analysis elucidated that hemoglobin and histocompatibility proteins and enzymes, which were associated with immune response, were closely associated with osteosarcoma. Transcription factors MYC and SP1 were predicted to be significantly related to osteosarcoma. The discovery of gene functions and transcription factors has the potential to use in clinic for diagnosis of osteosarcoma in future. In addition, it will pave the way to studying mechanism and effective therapies for osteosarcoma.

摘要

骨肉瘤是一种侵袭性恶性肿瘤,表现出成骨细胞分化并产生恶性类骨质。本研究的目的是寻找与骨肉瘤相关的特征基因以及能够区分癌组织与非肿瘤组织的相关基因功能。从基因表达综合数据库(GEO)下载基因表达谱GSE14359,其中包括10个骨肉瘤样本和2个正常样本。使用R语言的limma软件包鉴定骨肉瘤样本与正常样本之间的差异表达基因(DEG)。运用DAVID挖掘骨肉瘤相关基因,并分析基因功能的基因本体(GO)富集情况以及京都基因与基因组百科全书(KEGG)通路。然后,基于从STRING数据集收集的数据构建DEG相应的蛋白质-蛋白质相互作用(PPI)网络。进一步分析前10个DEG的主成分以及前20个DEG的PPI网络。最后,将两组DEG上传至TfactS数据库预测转录因子。共筛选出437个基因作为DEG,其中包括114个上调基因和323个下调基因,通过疾病模块分析,其中46个基因与骨肉瘤相关。GO和KEGG通路富集分析表明,这些基因主要影响免疫反应过程以及骨骼和血管系统的发育。PPI网络分析表明,与免疫反应相关的血红蛋白、组织相容性蛋白和酶与骨肉瘤密切相关。预测转录因子MYC和SP1与骨肉瘤显著相关。基因功能和转录因子的发现未来有可能用于临床诊断骨肉瘤。此外,这将为研究骨肉瘤的发病机制和有效治疗方法铺平道路。

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