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利用DNA微阵列技术筛选与人类胶质母细胞瘤相关的差异表达基因及功能分析

Screening of differentially expressed genes associated with human glioblastoma and functional analysis using a DNA microarray.

作者信息

Wang Lina, Wei Bo, Hu Guozhang, Wang Le, Bi Miaomiao, Sun Zhigang, Jin Ying

机构信息

Department of Ophthalmology, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.

Department of Neurosurgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.

出版信息

Mol Med Rep. 2015 Aug;12(2):1991-6. doi: 10.3892/mmr.2015.3659. Epub 2015 Apr 22.

Abstract

Glioblastoma multiforme (GBM) is the most malignant type of human glioma, and has a poor prognosis. Screening differentially expressed genes (DEGs) in brain tumor samples and normal brain samples is of importance for identifying GBM and to design specific-targeting drugs. The transcriptional profile of GSE30563, containing three genechips of brain tumor samples and three genechips of normal brain samples, was downloaded from Gene Expression Omnibus to identify the DEGs. The differences in the expression of the DEGs in the two different samples were compared through hierarchical biclustering. The co-expression coefficient of the DEGs was calculated using the information from COXPRESdb, the network of the DEGs was constructed and functional enrichment and pathway analysis were performed. Finally, the transcription factors of important DEGs were predicted. A total of 1,006 DEGs, including 368 upregulated and 638 downregulated DEGs, were identified. A close correlation was demonstrated between six important genes, associated with immune response, HLA-DQB1, HLA-DRB1, HLA-DPA1, HLA-B, HLA-DMA and HLA-DRA, and the immune response. Allograft rejection was selected as the most significant pathway. A total of 17 transcription factors, including nuclear factor (NF)-κB and NF-κB1, and their binding sites containing these six DEGs, were also identified. The DEGs, including major histocompatibility complex (MHC) class II, DQβ1, MHC class II, DRβ1, MHC class IB, MHC class II, DMα, MHC class II, DPα1, MHC class II, DRα, may provide novel targets for the diagnosis and treatment of GBM. The transcription factors of these six genes and their binding sites may also provide evidence and direction for identifying target-specific drugs.

摘要

多形性胶质母细胞瘤(GBM)是人类胶质瘤中最恶性的类型,预后较差。筛选脑肿瘤样本和正常脑样本中的差异表达基因(DEG)对于识别GBM和设计靶向药物具有重要意义。从基因表达综合数据库下载了包含三个脑肿瘤样本基因芯片和三个正常脑样本基因芯片的GSE30563转录谱,以识别DEG。通过层次双聚类比较了两种不同样本中DEG表达的差异。利用来自COXPRESdb的信息计算DEG的共表达系数,构建DEG网络并进行功能富集和通路分析。最后,预测了重要DEG的转录因子。共鉴定出1006个DEG,其中368个上调,638个下调。与免疫反应相关的六个重要基因HLA-DQB1、HLA-DRB1、HLA-DPA1、HLA-B、HLA-DMA和HLA-DRA与免疫反应之间存在密切相关性。同种异体移植排斥被选为最显著的通路。还鉴定出总共17种转录因子,包括核因子(NF)-κB和NF-κB1,以及包含这六个DEG的它们的结合位点。包括主要组织相容性复合体(MHC)II类、DQβ1、MHC II类、DRβ1、MHC IB类、MHC II类、DMα、MHC II类、DPα1、MHC II类、DRα在内的DEG可能为GBM的诊断和治疗提供新的靶点。这六个基因的转录因子及其结合位点也可能为识别靶向特异性药物提供证据和方向。

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