基于高通量芯片和生物信息学挖掘多发性骨髓瘤的发病差异基因

发布时间：2018-04-28 19:39

本文选题：多发性骨髓瘤 + 差异表达基因　；参考：《第二军医大学学报》2017年07期

【摘要】：目的筛选多发性骨髓瘤(MM)患者与正常人群之间的差异表达基因(DEGs),探究MM的发病机制,为MM的基因诊断和治疗提供导向。方法从GEO数据库中检索获取MM患者的芯片数据,通过Morpheus在线工具进行芯片数据质量控制和DEGs的筛选,运用DAVID数据库对筛选获得的DEGs行基因富集和通路分析,通过STRING数据库构建蛋白相互作用网络,并采用Cytoscape软件行模块分析。结果共获得16 211个DEGs,包括7 586个上调基因和8 625个下调基因(P0.05)。基因本体(GO)分析结果表明,生物学过程中上调DEGs主要涉及鞘糖脂代谢等30个功能簇,下调DEGs涉及细胞分裂等163个功能簇;分子功能中上调DEGs主要涉及蛋白质结合等29个功能簇,下调DEGs主要涉及组蛋白结合等59个功能簇;细胞成分中上调DEGs主要集中在细胞溶质等27个功能簇中,而下调DEGs主要集中在核质等78个功能簇中。京都基因与基因组百科全书(KEGG)分析结果表明,上调DEGs主要涉及溶酶体相关通路等26条通路,下调DEGs主要涉及DNA复制等27条通路。蛋白互作网络分析示CDK1、TOP2A、AURKB、BRCA1、CHEK1、PTEN、RAD51、GMPS、CDC45和CDKN2A 10个基因为富集程度最高的核心DEGs,模块分析显示得分最高的3个基因模块主要与核分裂、DNA复制和核酸代谢过程相关。结论通过多种生物信息学方法筛选获得了MM患者和健康对照组的DEGs,并从不同角度阐释了MM发病机制的相关基因及其表达特征,为MM特异性诊断标志和靶向治疗等提供了依据。
[Abstract]:Objective to screen the differentially expressed gene (DEGsN) between multiple myeloma (MM) patients and normal controls, to explore the pathogenesis of MM and to provide guidance for the gene diagnosis and treatment of MM. Methods the microarray data of MM patients were retrieved from the GEO database. The chip data quality control and DEGs screening were carried out by Morpheus online tools. The gene enrichment and pathway analysis of DEGs were performed by DAVID database. Protein interaction network was constructed by STRING database and analyzed by Cytoscape software line module. Results A total of 16 211 DEGs were obtained, including 7 586 up-regulated genes and 8 625 down-regulated genes (P0.05). The results of gene ontology analysis showed that up-regulated DEGs mainly involved 30 functional clusters such as sheath glycolipid metabolism, down-regulated DEGs related to cell division and so on, and up-regulated DEGs mainly related to 29 functional clusters such as protein binding in the molecular function, which was related to 30 functional clusters such as sheath glycolipid metabolism, down-regulation of DEGs and cell division. Down-regulation of DEGs mainly involves 59 functional clusters such as histone binding, up-regulation of DEGs in cell components is mainly concentrated in 27 functional clusters such as cell solute, while down-regulated DEGs is mainly concentrated in 78 functional clusters such as nuclear and cytoplasm. KEGG analysis of Kyoto gene and genome encyclopedia showed that up-regulation of DEGs mainly involved 26 lysosomal pathways and down-regulation of DEGs mainly involved 27 pathways such as DNA replication. Protein interaction network analysis showed that CDK1 / TOP2An AURKBU BRCA1 / CHEK1 / PTEK1 / RAD51 / GMPSCDC45 and CDKN2A had the highest concentration of core DEGs.The results showed that the three gene modules with the highest score were mainly related to the replication of mitotic DNA and the process of nucleic acid metabolism. Conclusion the DEGs of MM patients and healthy controls were obtained by various bioinformatics methods, and the related genes and their expression characteristics of MM pathogenesis were explained from different angles, which provided the basis for the specific diagnostic markers and targeted therapy of MM.
【作者单位】：第二军医大学海军医学系学员3队;第二军医大学长海医院脊柱外科;
【分类号】：R733.3

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