摘要
目的基于生物信息学分析软骨肉瘤的关键基因及发病机制。方法从GEO数据库获取人类软骨肉瘤相关基因芯片数据集GSE48418和GSE30835,包含17例软骨肉瘤患者样本和7例健康对照者样本。应用R语言软件进行差异表达基因(DEGs)分析。应用DAVID数据库对两个数据集共同的DEGs进行基因本体论(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。使用STRING数据库及Cytoscape软件,针对共同DEGs构建蛋白-蛋白相互作用网络,并利用Cytoscape软件筛选关键基因。结果两组芯片数据集的共同DEGs有62个,包含28个表达上调基因和34个表达下调基因。GO功能富集分析结果显示,共同DEGs富集在细胞与基质黏附、细胞与基质黏附的调节、肌细胞迁移、小梁形态发生、小梁组成等生物学过程,富集在含胶原的细胞外基质(ECM)、内质网腔、胶原三聚体等细胞组分,涉及糖胺聚糖结合、ECM结构成分提供的抗压支持、含硫化合物结合等分子功能。KEGG通路富集分析结果显示,DEGs与黏着力、磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)、ECM-受体相互作用等信号通路相关。筛选出COL1A1、COL3A1、FSTL1、THBS2、COL4A4、cyclin D1、CKAP4、CTHRC1、COL8A1及PLAU共10个关键基因。结论COL1A1、FSTL1、THBS2及cyclin D1等基因对软骨肉瘤的发生有重要作用,其可能通过调控ECM代谢和PI3K/AKT等信号通路来参与软骨肉瘤的发生。
Objective To analyze the key genes and pathogenesis of chondrosarcoma based on bioinformatics.Methods Gene chip datasets GSE48418 and GSE30835 related to human chondrosarcoma were obtained from the GEO database,including samples of 17 patients with chondrosarcoma and 7 healthy control individuals.The differentially expressed genes(DEGs)analysis was performed by employing R language software.The Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on common DEGs shared by both datasets by using DAVID database.The protein-protein interaction network was established for common DEGs by employing STRING database and Cytoscape software,and key genes were screened by using Cytoscape software.Results Two groups of chip datasets contained 62 common DEGs,including 28 up-regulated genes,and 34 down-regulated genes.The results of GO functional enrichment analysis revealed that common DEGs were enriched in the biological processes with respect to cell-substrate adhesion,regulation of cell-substrate adhesion,muscle cell migration,trabecula morphogenesis,trabecula formation,etc.,enriched in the cellular compositions in terms of collagen-containing extracellular matrix(ECM),endoplasmic reticulum lumen,and collagen trimers,etc.,and involved in the molecular functions of glycosaminoglycan binding,ECM structural constituent conferring tensile strength,and sulfur compound binding,etc.The results of KEGG pathway enrichment analysis interpreted that DEGs were related to signaling pathways of adhesion,phosphoinositide-3-kinase(PI3K)/protein kinase B(AKT),and ECM-receptor interaction,etc.A total of 10 key genes with respect to COL1A1,COL3A1,FSTL1,THBS2,COL4A2,cyclin D1,CKAP4,CTHRC1,COL8A1,and PLAU were screened out.Conclusion COL1A1,FSTL1,THBS2,cyclin D1,and other genes exert crucial effects in the occurrence of chondrosarcoma,it may be involved in the occurrence of chondrosarcoma by regulating ECM metabolism,PI3K/AKT,and other signaling pathways.
作者
沈琦玮
钟宗烨
SHEN Qiwei;ZHONG Zongye(Operating Room,Zhongshan Hospital Affiliated to Fudan University,Shanghai 200032,China;Operating Room,Shanghai Geriatrics Center,Shanghai 201100,China;Department of Rehabilitation Medicine,Zhongshan Hospital Affiliated to Fudan University,Shanghai 200032,China)
出处
《广西医学》
CAS
2023年第9期1060-1064,共5页
Guangxi Medical Journal
基金
上海市临床重点专科项目(shslczdzk02703)。
