基于生物信息学分析肾透明细胞肉瘤核心基因及免疫细胞浸润  

Core genes and immune cell infiltration of clear cell sarcoma of the kidney:a bioinformatics analysis

作　　者：江爱民 王安邦[1] 顾迪 董凯 富智斌 刘冰[1] 王林辉[1] JIANG Ai-min;WANG An-bang;GU Di;DONG Kai;FU Zhi-bin;LIU Bing;WANG Lin-hui(Department of Urology,Changzheng Hospital,Naval Medical University(Second Military Medical University),Shanghai 200003,China)

机构地区：[1]海军军医大学(第二军医大学)长征医院泌尿外科,上海200003

出　　处：《第二军医大学学报》2021年第5期503-511,共9页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(81872074),上海市科技创新行动计划(11951500).

摘　　要：目的基于基因表达汇编(GEO)数据库挖掘肾透明细胞肉瘤(CCSK)的核心基因并分析肿瘤和正常组织间免疫细胞浸润情况,为CCSK的诊疗提供新方向。方法对GEO数据库中GSE49972及GSE2712数据集进行联合分析,筛选CCSK和正常胚肾组织间的差异表达基因,并对差异表达基因进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)信号通路富集分析。构建蛋白质-蛋白质相互作用网络,鉴定CCSK的核心基因,同时对CCSK及正常胚肾组织进行免疫细胞浸润分析。结果共筛选出740个差异表达基因,GO功能富集分析结果显示这些差异表达基因集中在细胞外结构组织、细胞外胶原基质、细胞黏附分子结合等功能模块。KEGG信号通路分析结果显示差异表达基因参与的主要信号通路富集于PI3K/Akt信号通路、肿瘤转录失调、黏着斑、钙离子信号通路及肿瘤蛋白多糖等。蛋白质-蛋白质相互作用网络分析发现核心模块中密封蛋白家族和钙黏着蛋白家族权重较大。免疫细胞浸润分析发现大多数免疫细胞在CCSK组织中浸润程度低,但CD4 T细胞浸润程度较高。结论密封蛋白和钙黏着蛋白等相关通路及核心基因在CCSK中发挥重要作用,可作为潜在的治疗靶点。免疫检查点与特定激酶抑制剂的联合应用可能提高对CCSK的免疫治疗效果。Objective To identify the core genes of clear cell sarcoma of the kidney(CCSK)based on the Gene Expression Omnibus(GEO)database,and to analyze the immune cell infiltration between tumor and normal tissues,so as to provide a new direction for the diagnosis and treatment of CCSK.Methods Combined analysis of GSE49972 and GSE2712 datasets from GEO database was performed to screen the differentially expressed genes between CCSK and normal embryonic kidney tissues.The Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses of the differentially expressed genes were performed and the protein-protein interaction network was constructed to identify the core genes of CCSK.Meanwhile,the immune cell infiltration of CCSK and normal embryonic kidney tissues was analyzed.Results A total of 740 differentially expressed genes were screened out,and the GO function analysis showed that these genes were enriched in the extracellular structure organization,collagen-containing extracellular matrix,cell adhesion molecule binding and so on.The KEGG signaling pathway analysis showed that the major signaling pathways involved in differentially expressed genes mainly included in phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway,trancriptional misregulation in cancer,focal adhesion,calcium signaling pathway and proteoglycans in cancer.The protein-protein interaction network analysis showed that claudin family and cadherin family had large weighted values in the core modules.The immunity cell infiltration analysis showed that the infiltration of most immune cells was low in CCSK tissues,but the infiltration of CD4 T cells was relatively high.Conclusion Claudin and cadherin pathways and core genes play an important role in CCSK and can be potential therapeutic targets.The combination of immune checkpoints and specific kinase inhibitors may improve the immunotherapeutic effect of CCSK.

关 键 词：肾肿瘤 透明细胞肉瘤 密封蛋白 钙黏着糖蛋白类 免疫细胞浸润 

分 类 号：R737.11[医药卫生—肿瘤]