摘要
目的软组织肉瘤是一种罕见的肿瘤,且预后极差,需要深入研究分子机制促进新的治疗策略的发展。方法为了确定软组织肉瘤发生发展过程中的候选基因,我们从基因表达综合数据库下载了GSE2719基因芯片数据集。运用Perl软件和R软件整理数据,分析正常组织与癌组织的差异表达,筛选出具有统计学意义的基因,并用Oncomine数据库进行Meta分析。随后利用R软件对单基因进行差异分析及相关性分析。用STRING工具构建了蛋白质相互作用网络,并用Cytoscape进行了模块分析。基于TCGA数据进行了AZGP1的生存分析。结果共筛选出10个基因:AZGP1、CUX2、CXCL14、NCAM1、PCDH8、PLP1、SCG3、SCG5、SERPINA3、WIF1,其中AZGP1、CXCL14、PLP1、SERPINA3基因在正常组织与癌组织中的差异表达有统计学意义(均P<0.01)。Meta分析显示AZGP1、CXCL14、SERPINA3基因在肿瘤组织中比正常组织的显著下调(均P<0.05)。单基因差异分析发现AZGP1基因在各类分型中的低表达更显著。相关性分析示AZGP1和PRSS8、TM7SF2基因呈显著正相关性。差异基因的富集功能和途径包括细胞周期相变的调节、有丝分裂细胞周期相变的调控、细胞器裂变、细胞周期过程的负调控、细胞循环和DNA复制。肿瘤组织中AZGP1低表达与肉瘤患者较低的总生存相关。结论AZGP1基因在软组织肉瘤中表达下调,并可能影响患者总生存。
Objective Soft tissue sarcomas are exceptionally rare tumors with poor prognosis.Further study of molecular mechanisms is required to promote the development of new therapeutic strategies.Methods To identify candidate genes in the development of soft tissue sarcomas,we downloaded the GSE2719 dataset from the Gene Expression Omnibus.Perl script and R software were used to analyze the differential expression between normal tissue and cancer tissue,and the genes with statistical significance were screened out for meta analysis using Oncomine database.Subsequently,R software was used to analyze the difference and correlation.The protein interaction network(PPI)was constructed using STRING network and module analysis was carried out using Cytoscape.Survival analysis of AZGP1 was performed based on TCGA data.Results Ten genes were screened out:AZGP1,CUX2,CXCL14,NCAM1,PCDH8,PLP1,SCG3,SCG5,SERPINA3,WIF1.Four genes(AZGP1,CXCL14,PLP1,SERPINA3)had statistically significant differences in expression between normal and cancerous tissues(P<0.01).Compared with normal tissues,AZGP1,CXCL14 and SERPINA3 were significantly down-regulated in tumor tissues using Oncomine database.We found that the low expression of AZGP1 in various types was more significant.The correlation analysis showed that AZGP1 had significant positive correlation with PRSS8 and TM7SF2.GO analysis results showed that changes in biological processes(BP)of DEGs were significantly enriched in regulation of cell cycle phase transition,regulation of mitotic cell cycle phase transition,organelle fission,Cell cycle,and DNA replication.The survival analysis showed that low expression ofAZGP1 was associated with lower overall survival in sarcoma patients.Conclusions In this study,AZGP1 was found to be down-regulated in soft tissue sarcoma and may affect the overall survival rate of patients.
作者
周亦一
何夕
刘俊
林明钦
焦晓栋
Zhou Yiyi;He Xi;Liu Jun;Lin Mingqin;Jiao Xiaodong(IDepartment of Oncology,Shanghai Changzheng Hospital,Shanghai 200003,China)
出处
《中华转移性肿瘤杂志》
2021年第2期123-130,共8页
Chinese Journal of Metastatic Cancer