肺腺癌EMT相关基因筛选及其ceRNA网络构建  

Screening of EMT-related genes in lung adenocarcinoma and construction of ceRNA network

作　　者：马楚涵 孙家琰 赵雨馨 赵幼敏 刘奕墨 赵子涵 王子剑 尹智华[3] MA Chuhan;SUN Jiayan;ZHAO Yuxin;ZHAO Youmin;LIU Yimo;ZHAO Zihan;WANG Zijian;YIN Zhihua(First Clinical College,China Medical University,Shenyang,Liaoning 110122,China;Fourth Clinical College,China Medical University,Shenyang,Liaoning 110122,China;School of Public Health,China Medical University,Shenyang,Liaoning 110122,China;School of Health Management,China Medical University,Shenyang,Liaoning 110122,China)

机构地区：[1]中国医科大学第一临床学院,辽宁沈阳110122 [2]中国医科大学第四临床学院,辽宁沈阳110122 [3]中国医科大学公共卫生学院,辽宁沈阳110122 [4]中国医科大学健康管理学院,辽宁沈阳110122

出　　处：《国际检验医学杂志》2023年第24期2954-2962,共9页International Journal of Laboratory Medicine

基　　金：国家级大学生创新创业计划训练项目(202210159003)。

摘　　要：目的筛选肺腺癌上皮间质转化(EMT)相关基因,并对其进行功能富集分析及蛋白互作网络(PPI)构建,根据竞争性内源RNA(ceRNA)假说及基因表达对患者预后的影响构建ceRNA网络。方法利用基因表达图谱及肿瘤基因组图谱数据库筛选肺腺癌组织与正常组织的差异表达基因,将其导入GenClip3,得到EMT相关基因;应用Metascape对其进行基因本体论及京都基因和基因组百科全书富集分析,并且通过STRING数据库构建PPI并获得EMT关键基因;利用Kaplan-Meier分析关键基因与患者预后的关系;使用miRTarbase、miRNet database、ENCORI等分析工具构建ceRNA网络。结果本研究获得了156个肺腺癌EMT相关基因及其关键基因钙黏蛋白1、白细胞介素-6、基质金属蛋白酶9、血小板内皮细胞黏附分子、细胞周期蛋白依赖性激酶抑制剂2A、α1-Ⅰ型胶原基因、分泌型磷酸蛋白1、TIMP基质金属蛋白酶抑制因子1、小窝蛋白1、zeste基因增强子同源物2(EZH2),并预测了关键基因的PPI及共同靶向这些关键基因的治疗性中药丹参、人参芦、人参、人参叶、人参花;构建了EZH2/hsa-miR-101-3p/GSEC预后相关ceRNA调控网络。结论本研究利用生物信息学方法系统描述了EMT过程中的基因相互作用,根据肺腺癌患者临床数据构建了EMT过程的预后相关ceRNA网络,为肺腺癌的治疗和预后判断提供了新思路。Objective To screen the epithelial mesenchymal transformation(EMT)-related genes in lung adenocarcinoma,perform functional enrichment analysis and construct protein interaction network(PPI).According to the competitive endogenous RNA(ceRNA)hypothesis and the effect of gene expression on the prognosis of patients,the ceRNA network was constructed.Methods The differentially expressed genes between lung adenocarcinoma tissues and normal tissues were screened by gene expression map and tumor genome map database,and the genes were imported into GenClip3 to obtain EMT-related genes.Metascape was used to perform gene ontology and Kyoto encyclopedia of gene and genome enrichment analysis,and STRING database was used to construct PPI and obtain EMT key genes.The relationship between key genes and prognosis was analyzed by Kaplan-Meier analysis.Analysis tools such as miRTarbase,miRNet database,and ENCORI were used to construct ceRNA networks.Results In this study,156 lung adenocarcinoma EMT-related genes and their key genes cadherin 1,interleukin-6,matrix metalloproteinase-9,platelet endothelial cell adhesion molecule,cyclin-dependent kinase inhibitor 2A,α1-Ⅰcollagen gene,secreted phosphoprotein 1,TIMP inhibitor of matrix metalloproteinase-1,caveolin-1 and Zeste homologue enhance core 2(EZH2)-1 were identified.The PPI of key genes was predicted,and the therapeutic drugs targeting these key genes including salvia miltiorrhiza,ginseng lu,ginseng leaf and ginseng flower were also predicted.The prognostic ceRNA regulatory network of EZH2/hsa-miR-101-3p/GSEC was constructed.Conclusion This study describes using bioinformatics methods system in the process of EMT gene interactions,according to the lung adenocarcinoma patients clinical data to construct the prognosis of the EMT process related ceRNA network,for the treatment and prognosis of lung adenocarcinoma judgment provides a new way of thinking.

关 键 词：上皮间质转化 关键基因 竞争性内源RNA 

分 类 号：R734.2[医药卫生—肿瘤]