基于加权基因共表达网络的复方红豆杉胶囊治疗肺腺癌有效成分及作用机制分析  

Effective components and mechanism of compound Taxus capsule in treatment of lung adenocarcinoma based on weighted gene co-expression network

作　　者：张泽鑫 余佳蓓 林思其 刘紫凤 陈林静 陈栩静 陈祎琦 ZHANG Zexin;YU Jiabei;LIN Siqi;LIU Zifeng;CHEN Linjing;CHEN Xujing;CHEN Yiqi(The First Clinical College of Guangzhou University of Chinese Medicine,Guangzhou 510006,China;不详)

机构地区：[1]广州中医药大学第一临床医学院,广州5100062 [2]广州中医药大学第二临床医学院

出　　处：《山东医药》2022年第5期16-20,共5页Shandong Medical Journal

基　　金：广州中医药大学大学生创新创业校级项目(X202110572148)。

摘　　要：目的基于加权基因共表达网络(WGCNA)分析复方红豆杉胶囊治疗肺腺癌(LUAD)的有效成分及作用机制。方法使用TCMSP数据库、BATMAN数据库筛选复方红豆杉胶囊的活性成分及治疗靶点;使用TCGA数据库及GEO数据库对LUAD的表达谱数据进行WGCNA分析,筛选LUAD的共表达模块。将复方红豆杉胶囊活性成分治疗靶点、TCGA数据库及GEO数据库中相关性差异最大的基因模块进行相互映射,取交集获得复方红豆杉胶囊治疗LUAD的加权共表达基因;使用R语言绘制加权共表达基因的药物—化合物—靶点图,并对加权共表达基因进行GO功能和KEGG通路富集分析。使用R语言对TCGA数据库的临床数据进行生存分析,绘制Kaplan-Meier单变量生存分析图,筛选复方红豆杉胶囊治疗LUAD的核心靶基因,并通过HPA数据库对该核心靶基因进行免疫组化分析,验证其在正常组织及LUAD组织中是否有差异。结果共得到复方红豆杉胶囊活性成分141个,作用靶点356个。TCGA数据库中共得到15个基因共表达模块,GEO数据库中共得到5个基因共表达模块,其中TCGA数据库中的绿松石色模块(正常样本r=0.77,LUAD样本r=-0.77,P=9E-119)及GEO数据库中的绿松石色模块(正常样本r=0.88,LUAD样本r=-0.88,P=5E-22)相关性差异最明显,分别包含了6587、649个基因。将复方红豆杉胶囊活性成分治疗靶点、GEO数据库绿松石色基因、TCGA数据库绿松石色基因取交集,共得到复方红豆杉胶囊治疗LUAD的加权共表达基因14个,分别为LDLR、FOS、IL6、CAV1、TUBB3、TUBB6、MCL1、CA2、JUN、SLC6A4、CD36、ALDH1A1、MAOB、TFAP2C。加权共表达基因的药物—化合物—靶点图显示,红豆素A和紫杉碱为复方红豆杉胶囊治疗LUAD的主要活性成分。GO功能分析显示,复方红豆杉胶囊治疗LUAD的主要生物过程为有机羟基化合物转运、细胞对氧化应激的反应、对脂多糖的反应等,主要细胞成分为内吞囊泡膜、内吞�Objective To analyze the effective components and mechanism ofcompound Taxus capsule in the treatment of lung adenocarcinoma(LUAD)based on weighted gene co-expression network(WGCNA).Methods TCMSP database and BATMAN database were used to screen the active components and therapeutic targets of compound Taxus capsule.TCGA database and GEO database were used to analyze the expression profile data of LUAD by WGCNA,and the genes of co-expression modules in LUAD were screened.The therapeutic targets of the active ingredients of compound Taxus capsule,the gene modules with the largest correlation difference in the TCGA database and the GEO database were mapped to each other,and the intersection was taken to obtain the weighted co-expression genes of compound Taxus capsule for the treatment of LUAD.The drug-compound-target map of the weighted co-expressed genes was drawn by R language,and GO function and KEGG pathway enrichment of weighted co-expressed genes were analyzed.The R language was used to analyze the survival of the clinical data in TCGA database.We drew the Kaplan-Meier univariate survival analysis diagram,screened the core target gene of compound Taxus capsule in the treatment of LUAD,and performed immunohistochemical analysis on the core target gene through HPA database to verify whether it was different in the normal tissues and LUAD tissues.Results A total of 141 active ingredients and 356 targets of compound Taxus capsule were obtained.A total of 15 gene co-expression modules were obtained from the TCGA database,and 5 gene co-expression modules were obtained from the GEO database.The correlation difference between Turquoise module in TCGA database(normal sample r=0.77,LUAD sample r=-0.77,P=9E-119)and Turquoise module in GEO database(normal sample r=0.88,LUAD sample r=-0.88,P=5e-22)was the most obvious,and they contained 6587 and 649 genes,respectively.By taking the intersection of the active ingredients of compound Taxus capsules,the turquoise color gene of GEO database,and the turquoise color gene of TCG

关 键 词：加权基因共表达网络分析 生物信息学 复方红豆杉胶囊 肺腺癌 分子靶点 信号通路 

分 类 号：R229[医药卫生—中医基础理论]