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对表达谱数据的分析确定了肝细胞癌中的关键基因和通路。

Analysis of expression profile data identifies key genes and pathways in hepatocellular carcinoma.

作者信息

Jiang Xuwei, Hao Yuqing

机构信息

Department of General Surgery, Shanghai, Baoshan District Hospital of Integrated Traditional and Western Medicine, Shanghai 201900, P.R. China.

出版信息

Oncol Lett. 2018 Feb;15(2):2625-2630. doi: 10.3892/ol.2017.7534. Epub 2017 Dec 6.

Abstract

The aims of the present study were to identify key genes and pathways associated with hepatocellular carcinoma (HCC) progression and predict compounds potentially associated with this type of carcinogenesis. The gene expression profile data of the GSE49515 dataset was obtained from the Gene Expression Omnibus database. The limma software package was used to identify the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Biological Networks Gene Ontology tool and the Database for Annotation, Visualization and Integrated Discovery, respectively. The Michigan Molecular Interactions database plugin within the Cytoscape software platform was used to perform protein-protein interaction (PPI) network analysis. Chemical-gene interaction data for HCC were obtained from the Comparative Toxicogenomics Database to evaluate the associations between drugs and specific genes. A total of 302 DEGs, including 231 downregulated and 71 upregulated, were identified. Cytokine-cytokine receptor interaction and chemokine signaling were the significantly enriched pathways. Additionally, PPI network analysis indicated a total of 13 highest degree hub nodes, including FBJ murine osteosarcoma viral oncogene homolog (FOS) and DNA damage-inducible transcript 3 protein (DDIT3). Chemical-gene interaction analysis revealed that and were targeted by >500 compounds, while >200 genes were targeted by 2,3,7,8-tetrachlorodibenzodioxin and benzo(α)pyrene. In conclusion, the present study demonstrated that , , the cytokine-cytokine receptor interaction pathway and the chemokine signaling pathway may be key genes and pathways associated with the development of HCC. Furthermore, exposure to 2,3,7,8-tetrachlorodibenzodioxin or benzo(α)pyrene may lead to hepatocarcinogenesis.

摘要

本研究的目的是鉴定与肝细胞癌(HCC)进展相关的关键基因和通路,并预测可能与这种致癌作用相关的化合物。GSE49515数据集的基因表达谱数据是从基因表达综合数据库中获取的。使用limma软件包来鉴定差异表达基因(DEG)。分别使用生物网络基因本体工具和注释、可视化与整合发现数据库进行基因本体和京都基因与基因组百科全书通路富集分析。利用Cytoscape软件平台中的密歇根分子相互作用数据库插件进行蛋白质-蛋白质相互作用(PPI)网络分析。从比较毒理基因组学数据库中获取HCC的化学-基因相互作用数据,以评估药物与特定基因之间的关联。共鉴定出302个DEG,包括231个下调基因和71个上调基因。细胞因子-细胞因子受体相互作用和趋化因子信号传导是显著富集的通路。此外,PPI网络分析表明共有13个最高度的枢纽节点,包括FBJ小鼠骨肉瘤病毒癌基因同源物(FOS)和DNA损伤诱导转录3蛋白(DDIT3)。化学-基因相互作用分析显示,[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称]被>500种化合物靶向,而>200个基因被2,3,7,8-四氯二苯并二恶英和苯并(α)芘靶向。总之,本研究表明,[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]、细胞因子-细胞因子受体相互作用通路和趋化因子信号传导通路可能是与HCC发生发展相关的关键基因和通路。此外,接触2,3,7,8-四氯二苯并二恶英或苯并(α)芘可能导致肝癌发生。

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