滑膜肉瘤差异表达基因生物信息学分析  

Bioinformatics analysis of differentially expressed genes in synovial sarcoma

作　　者：王庆宇[1] 林菲菲[1] 陈高扬[1] 李照彦 杨麒巍 杜珍武[1] 张桂珍[1] 宋旸[1] WANG Qingyu;LIN Feifei;CHEN Gaoyang;LI Zhaoyan;YANG Qiwei;DU Zhenwu;ZHANG Guizhen;SONG Yang(The Second Hospital of Jilin University,Department of Orthopaedics,Changchun 130041,China)

机构地区：[1]吉林大学第二医院骨科,长春130041

出　　处：《中国体视学与图像分析》2018年第3期260-270,共11页Chinese Journal of Stereology and Image Analysis

基　　金：国家自然科学基金(No.81702195);吉林省精准医学分子诊断应用示范项目(2016-2018;NDRC);吉林省卫计委项目(No.20180520125JH);吉林省教育厅项目(No.JJKH20170853KJ);吉林省科技厅项目(20180520111JH);吉林大学白求恩青年基金项目(No.2015409)

摘　　要：目的通过生物信息学分析方法筛选滑膜肉瘤组织中关键lncRNA、microRNAs和mRNA,阐述其互相作用机制以及关键信号通路。方法通过Gene Expression Omnibus(GEO)在线数据库检索并下载人滑膜肉瘤转录组数据,并应用基因本体论分析(Gene Ontology,GO)、京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)、竞争性内源RNA(competing endogenous RNAs,ceRNAs)互作网络分析和蛋白互作网络分析(Protein-Protein Interaction,PPI)对差异表达基因进行深入分析。结果共4个数据集纳入本项研究包括GSE28866,GSE18546,GSE2719和GSE42977,包含21个滑膜肉瘤组织和56个正常对照组织,在这些数据集中共获取了12个差异表达的lncRNA,119个差异表达的miRNA和1637个差异表达的mRNA。构建ceRNA调控网络并展示lncRNA-miRNA-mRNA之间的调控作用,发现6个lncRNA (RP11-123K19. 1,RP11-261N11. 8,MEG3,FOXD2-AS1,CTD-2228K2. 7,LINC00982)和7个miRNA(hsa-miR-142-5p,hsamiR-548c-3p,hsa-miR-1224-5p,hsa-miR-133b,hsa-miR-206,hsa-miR-378-3p,hsa-miR-765)在滑膜肉瘤病变中具有重要作用。KEGG分析示滑膜肉瘤病变与47个信号通路显著相关(P <0. 05),特别是癌症中转录失调的信号通路(P=5. 56×10-8)。PPI互作网络分析展示了154种蛋白质,6种转录因子和10个信号通路之间的相互作用。结论通过对在线数据库进行生物信息学分析,滑膜肉瘤的多个关键分子靶点和信号通路被确认,有助于对滑膜肉瘤病变分子发病机制进行深入研究。Objective The differently expressed lncRNA, microRNAs and mRNA in synovial sarcoma （SS） were screened by bioinformatics analysis, and the interaction mechanism and key signaling pathways were further analyzed. Methods Human synovial sarcoma-associated expression profiles datasets were retrieved and downloaded from the Gene Expression Omnibus （GEO） online database, and Gene Ontology （ GO）, Kyoto Encyclopedia of Genes and Genomes （ KEGG）, endogenous competitive RNAs （ceRNAs） interaction network analysis and protein-protein interaction （PPI） network were used to further analyze differentially expressed genes. Results The expression profiles of GSE28866, GSE18546, GSE2719 and GSE42977, including 21 SS and 56 normal tissues, were downloaded from Gene Expression Omnibus （GEO） database and deeply analyzed. A total of 12 differentially expressed lncRNAs, 119 differentially expressed miRNAs and 1637 differentially expressed mRNAs were identified from the four datasets. Based on differentially expressed genes above, a ceRNA network was constructed and it showed that 6 lncRNA （RPll-123K19.1, RPll-261Nll. 8, MEG3 FOXD2-AS1, CTD-2228K2.7, LINC00982） and 7 miRNAs （hsa-miR-142-Sp, hsa-miR-548c-3p, hsa-miR- 1224-5p, hsa-miR- 133b, hsa-miR- 206, hsa-miR-378-3p, hsa-miR-765） were highly related to SS. Pathway analyses demonstrated the ceRNA network was significant associated with 47 pathways （P〈0. 05） , particularly pathway of transcrip-tional disorder in cancer （P= 5.56×10^-8）. The interactions between 154 proteins, 6 transcription factors and 10 signaling pathways were further analyzed in the PPI network. Conclusions By bioinformatics a- nalysis of online databases, multiple key molecular targets and signaling pathways of synovial sarcoma are confirmed, which contributes to the in-depth study of the molecular pathogenesis of synovial sarcoma lesions.

关 键 词：长链非编码RNA 生物信息学分析 ceRNA 滑膜肉瘤 

分 类 号：R446.8[医药卫生—诊断学] R604[医药卫生—临床医学]