非小细胞肺癌间充质干细胞差异性模块筛选和功能分析

Differential module screening and functional analysis of non-small cell lung cancer mesenchymal stem cells

目的:通过筛选间充质干细胞特异共表达的基因簇分析非小细胞肺癌(NSCLC)间充质干细胞(MSCs)在NSCLC发生、发展的分子机制和潜在的治疗靶标。方法:基于GEO高通量基因表达谱数据,采用模块药理学平台构建NSCLC-MSCs基因共表达网络,通过Z_(summary)、ME特征参数精细化筛选NSCLC-MSCs差异模块。对差异性模块的基因簇进行GO功能分析和KEGG通路富集分析,并通过生存分析、药物靶标筛选等方法分析差异性模块中不同功能基因对肺癌的治疗和预后价值。结果:研究共得到46个NSCLC-MSCs共表达模块,与正常肺组织(NLT)-MSCs相比共得到3个差异模块分别为29号、33号、35号,共计492个基因。功能富集分析表明,29号模块主要与细胞调控和适应性响应有关,33号模块与细胞免疫调节相关,35号模块主要与细胞代谢调控相关。通过分析发现差异模块中有79(16.1%)个药物靶标相关的调控基因,有372个(70.5%)是预后显著性(P<0.01)的预后相关基因,说明差异模块中的基因簇在疾病治疗和预后方面具有重要价值。结论:模块药理学平台可以筛选识别出NSCLC-MSCs特异性相关差异模块,为精细化筛选药物靶标和预后标志物提供方法和手段。

Objective:To analyze the differential modules of mesenchymal stem cells(MSCs)in non-small cell lung cancer(NSCLC),in order to explore the role of differential modules in the molecular mechanism of the occurrence and development of NSCLC and potential therapeutic targets.Methods:Based on GEO high-throughput gene expression profiling data,NSCLC-MSCs gene co-expression network was constructed using module pharmacology platform,and different modules were screened by Z_(summary)and ME values.GO function analysis and KEGG pathway enrichment analysis were performed on the differential modules.The treatment and prognostic value of different functional genes on lung cancer in the differential modules were analyzed through survival analysis and drug target screening and other methods.Results:A total of 46 NSCLC-MSCs co-expression modules were obtained.Modules No.29,33 and 35 were selected as NSCLC-MSCs differentiation modules.Modules 29,33 and 35 had 175,161 and 156 genes respectively.Module 29 was mainly related to cell regulation and adaptive response,module 33 was related to cellular immune regulation,and module 35 was mainly related to cell metabolic regulation.There were 26,25 and 28 genes in modules 29,33 and 35 that were drug targets respectively.Prognostic analysis showed that 129,105 and 113 genes in modules 29,33 and 35 showed significant prognostic significance(P<0.01).It was found that 79(16.1%)regulatory genes related to drug targets and 372(70.5%)prognostic genes were significant(P<0.01),indicating that gene clusters in the differential modules have important value in disease treatment and prognosis.Conclusion:The modular pharmacology platform of this study can screen and identify NSCLC-MSCs specific related differential modules,providing method for fine screening of drug targets and prognostic markers.