Identification of key pathways and genes in nasopharyngeal carcinoma using bioinformatics analysis
Identification of key pathways and genes in nasopharyngeal carcinoma using bioinformatics analysis
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利用生物信息学分析识别鼻咽癌的关键通路和基因
DOI：
10.3892/ol.2019.10133
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发表时间：
2019-05-01
期刊：
影响因子：
2.9
通讯作者：
Yin, Li
中科院分区：
文献类型：
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作者：
Zhu, Hong-Ming;Fei, Qian;Yin, Li
鼻咽癌是头颈部最常见的恶性肿瘤之一。本研究的目的是通过生物信息学分析确定参与NPC的关键通路和基因，并确定NPC增殖和进展的潜在分子机制。从Gene Expression Omnibus数据库下载三个基因表达谱（GSE 12452、GSE 34573和GSE 64634）。共分析了76个样本，其中59个为NPC样本，17个为正常样本。随后进行基因本体（GO）和京都基因和基因组百科全书（KEGG）途径富集分析。利用Cytoscape软件构建差异表达基因的蛋白质相互作用网络。对GSE 12452、GSE 34573和GSE 64634数据集的分析分别鉴定了1，301（553个上调和748个下调）、1，232（348个上调和884个下调）和1，218（555个上调和663个下调）DEG。使用文氏图分析，选择涵盖所有三个数据集的268个DEG（59个上调和209个下调）用于进一步分析。GO分析结果显示，上调的DEGs在细胞粘附、细胞分裂、有丝分裂和有丝分裂细胞周期等生物学过程中显著富集。表达下调的DEGs主要集中在微管运动、纤毛运动、纤毛轴丝组装和上皮细胞分化等方面。KEGG通路分析结果显示，DEG表达上调与细胞外基质-受体相互作用、人乳头瘤病毒感染、致炎性右室心肌病和局灶性粘连等通路密切相关，而DEG表达下调则与代谢途径、亨廷顿病、流体剪切力和动脉粥样硬化以及化学致癌作用密切相关。基于DEG的PPI网络，鉴定了以下前10个枢纽基因：动力蛋白轴丝轻中间链1，动力蛋白轴丝中间链2，钙调蛋白1，含有卷曲螺旋结构域114，动力蛋白轴丝重链5，放射状辐头9同系物，放射状辐头组分4A，NDC 80动粒复合体组分，胸苷酸合成酶和卷曲螺旋结构域含有39.总之，通过对DEG进行全面的生物信息学分析，确定了可用于阐明NPC潜在分子机制的推定靶标。
Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in the head and neck. The aim of the current study was to identify the key pathways and genes involved in NPC through bioinformatics analysis and to identify potential molecular mechanisms underlying NPC proliferation and progression. Three gene expression profiles (GSE12452, GSE34573 and GSE64634) were downloaded from the Gene Expression Omnibus database. A total of 76 samples were analyzed, of which 59 were NPC samples and 17 were normal samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently conducted. The protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed using Cytoscape software. Analysis of GSE12452, GSE34573 and GSE64634 datasets identified 1,301 (553 upregulated and 748 downregulated), 1,232 (348 upregulated and 884 downregulated) and 1,218 (555 upregulated and 663 downregulated) DEGs, respectively. Using Venn diagram analysis, 268 DEGs (59 upregulated and 209 downregulated) that intersected all three datasets, were selected for further analysis. The results of GO analysis revealed that upregulated DEGs were significantly enriched in biological processes, including cell adhesion', cell division', mitosis' and mitotic cell cycle'. The downregulated DEGs were mainly enriched in microtubule-based movement', cilium movement', cilium axoneme assembly' and epithelial cell differentiation'. The KEGG pathway analysis results revealed that the upregulated DEGs were highly associated with several pathways, including extracellular matrix-receptor interaction', human papillomavirus infection', arrhythmogenic right ventricular cardiomyopathy' and focal adhesion', whereas the downregulated DEGs were enriched in metabolic pathways', Huntington's disease', fluid shear stress and atherosclerosis' and chemical carcinogenesis'. On the basis of the PPI network of the DEGs, the following top 10 hub genes were identified: Dynein axonemal light intermediate chain 1, dynein axonemal intermediate chain 2, calmodulin 1, coiled-coil domain containing 114, dynein axonemal heavy chain 5, radial spoke head 9 homolog, radial spoke head component 4A, NDC80 kinetochore complex component, thymidylate synthetase and coiled-coil domain containing 39. In conclusion, by performing a comprehensive bioinformatics analysis of DEGs, putative targets that could be used to elucidate the molecular mechanisms underlying NPC were identified.