文章摘要
张明光,齐晓光,徐海军.基于 GEO和 TCGA数据库筛选恶性胸膜间皮瘤免疫治疗疗效预测关键基因[J].安徽医药,2023,27(1):135-139.
基于 GEO和 TCGA数据库筛选恶性胸膜间皮瘤免疫治疗疗效预测关键基因
Identification of candidate genes predicting the response to immunotherapy for malignant pleural mesothelioma based on GEO and TCGA database
  
DOI:10.3969/j.issn.1009-6469.2023.01.030
中文关键词: 间皮瘤  胸膜  高通量基因表达(GEO)数据库  免疫治疗  生物信息学  TCGA数据库  程序性死亡受体 1  细胞毒性 T淋巴细胞相关蛋白 4
英文关键词: Mesothelioma  Pleura  GEO database  Immunotherapy  Bioinformatics  TCGA database  Programmed cell death 1(PD-1)  Recombinant cytotoxic T-lymphocyte associated antigen 4(CTLA-4)
基金项目:
作者单位E-mail
张明光 亳州市中医院肿瘤内科安徽亳州236800  
齐晓光 解放军总医院肿瘤内科北京 100853  
徐海军 亳州市中医院肿瘤内科安徽亳州236800 xuhaijun11973@163.com 
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中文摘要:
      目的探索免疫治疗在恶性胸膜间皮瘤( malignant pleural mesothelioma,MPM)中免疫疗效相关关键分子及其可能的机制。方法 2018年 7月至 2020年 7月,纳入 GEO数据库中 GSE117358的表达谱进行分析;首先,根据是否对免疫治疗是否有效分为两组:免疫治疗反应组和免疫治疗无反应组,同时分析两组之间差异有统计学意义基因;其次,分析两组差异有统计学意义基因在基因本体( gene ontology,GO)生物学行为及京都基因与基因组百科全书( Kyoto encyclopedia of genes and genomes,KEGG)富集信号通路等方面的差异;最后,对差异有统计学意义基因构建蛋白 -蛋白互作网络,筛选在生物学行为中的重要模块及关键基因,并对关键基因在 TCGA数据库中进行整合分析验证。结果在免疫治疗反应组( 12个样本)及免疫治疗无反应组( 12个样本)中共筛选出 1 025个差异基因,相对于免疫治疗无反应组,在免疫治疗反应组中有 782个上调和 243个下调基因。 GO和 KEGG分析显示,这些差异基因的功能主要集中在细胞因子受体通路、细胞黏附通路、 T细胞受体通路及 NF-kappa B信号通路等;在蛋白 -蛋白互作网络分析中,筛选出节点度最高的 10个核心基因包括 Tnf,Il6,Ptprc,Csf2,Cd86,Cxcl9, Sell,Cxcr3,Ccl2,Cd40。TCGA数据库整合分析显示, Tnf,Il6,Cd86,Cxcl9,Sell,Cxcr3,Cd40等疗效相关关键基因在肉瘤样胸膜间皮瘤中呈现相对高表达,且差异有统计学意义。结论核心基因 Tnf,Il6,Ptprc,Csf2,Cd86,Cxcl9,Sell,Cxcr3,Ccl2,Cd40有望成为预测 MPM的分子标志物及治疗的潜在靶点。
英文摘要:
      Objective To identify the key genes associated with immune efficacy in the treatment of malignant pleural mesothelioma(MPM) and the likely mechansim.Methods The expression profile of GSE117358 obtained from GEO database was analyzed from July 2018 to July 2020. Firstly, according to the response to immunotherapy, patients were assigned into response group and non-responsegroup. Meanwhile, differentially expressed genes (DEGs) were screened. Secondly, Gene Ontology (GO) and Kyoto encyclopedia ofgenes and genomes (KEGG) analyses were performed to analyze the differences in biological behavior and enrichment signaling pathways between the two groups. Finally, protein-protein interaction network (PPI) was constructed, and then the important modules andkey genes in biological behavior were screened. In addition, the key genes were analyzed and verified in the TCGA database.Results In total, 1 025 DEGs were screened between the response group (12 samples) and the non-response group (12 samples). There were 782 up-regulated and 243 down-regulated genes in the response group in comparison with the non-response group. GO and KEGG analysisresults showed that the functions of these DEGs focused mainly on the cytokine receptor pathway, cell adhesion pathway, T cell receptor pathway and NF-kappa B signaling pathway. In the PPI analysis, the top 10 core genes (Tnf, Il6, Ptprc, Csf2, Cd86, Cxcl9, Sell, Cxcr3, Ccl2, Cd40) with high node degree were screened. TCGA database integration analysis results showed that the expressions of Tnf,Il6, Cd86, Cxcl9, Sell, Cxcr3 and Cd40 genes were higher in the subtype of sarcomatoid mesothelioma than those in other subtypes withstatistically significant difference.Conclusion The core genes Tnf, Il6, Ptprc, Csf2, Cd86, Cxcl9, Sell, Cxcr3, Ccl2, Cd40 in these important modules might become novel predictive markers for immunotherapy and potential therapeutic targets in MPM.
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