基于Limma及功能富集探究复方金果胃康散治疗胃癌的作用机制  

Therapeutic Effect of Compound Jinguo Weikang Powder on Gastric Cancer:Based on Limmaand Functional Enrichment

作　　者：宋健[1] 孟凯强 杜娟 袁敏惠 白宇雪 常梦瑶 王捷虹 杜晓泉 杨志宏 沈舒文[1] SONG Jian;MENG Kai-qiang;DU Juan;YUAN Min-hui;BAI Yu-xue;CHANG Meng-yao;WANG Jie-hong;DU Xiao-quan;YANG Zhi-hong;SHEN Shu-wen(Shaanxi University of Chinese Medicine,Xianyang Shaanxi 712046;Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang Shaanxi 712000)

机构地区：[1]陕西中医药大学,陕西咸阳712046 [2]陕西中医药大学附属医院,陕西咸阳712000

出　　处：《世界中西医结合杂志》2022年第7期1283-1289,共7页World Journal of Integrated Traditional and Western Medicine

基　　金：全国名老中医药专家传承工作室建设项目(国中医药人教发[2016]42号);第六批全国老中医药专家学术经验继承工作项目(国中医药人教发[2017]29号);陕西省大学生创新创业训练计划项目(S202110716040);陕西省教育厅专项科学研究计划项目(18JK0225);陕西中医药大学科研计划项目(2017PY09)。

摘　　要：目的旨在通过广义线性模型的差异表达筛选及功能富集探究复方金果胃康散在胃癌的治疗作用,为后续开展中药治疗癌症提供基础研究方向和临床的理论基础。方法从TARGET数据库下载胃癌患者临床信息和测序RNA数据。通过中国知网等文献数据库及TCMSP对复方金果胃康散所有中药的有效成分及蛋白进行收集整理,运用Excel、计算机R语言基本算法整理复方金果胃康散的蛋白质,将TARGET导出的胃癌患者样本数据整理后进行聚类分析,再通过计算机R语言构建Limma和功能富集从而分析治疗作用。结果复方金果胃康散7种药物包含有效成分1814种,蛋白358种。TARGET中共获得443个胃癌患者的样本,表达谱共获得27226个基因,剔除了部分数据不全的样本,最后在407个样本中进行数据分析,将复方金果胃康散与胃癌患者取交集共获得352个基因。根据单因素Cox分析产生的352个预后基因,采用一致聚类方法将胃癌患者分为C1和C2两个亚组。175例患者被聚类为聚类1,232例患者被聚类为聚类2。Limma分析结果为差异倍数为1.2的前提下,发现了98个上调基因,70个下调基因。KEGG结果显示复方金果胃康散基因主要在癌症通路富集,并且能富集多种癌症通路,PPI分析确定了8个亚模型。GSEA显示DNA损伤反应对miRNA的调控、巨型BII淋巴细胞上升、DNA损伤反应、肝癌、P75-NTR通路和ATM-信号通路等相关。结论复方金果胃康散作为沈舒文教授和宋健副教授在胃癌治疗的临床常用方,从分子角度数据结果显示复方金果胃康散对胃癌有很好的治疗作用,同时也阐明了在分子层面复方金果胃康散治疗作用的机制途径。Objective Compound Jinguo Weikang Powder is a common clinical prescription for gastric cancer,which displays remarkable efficacy in cancer research and clinical settings and is often used for cancer prognosis.However,a few basic studies of effect of this prescription on cancer metastasis areavailable.Limma isa software package for the analysis of gene expression microarray data,especially the use ofgeneralized linear model for the assessment of differential expression,and functional enrichment analysis is a conventional bioinformatics method to study“drugs-diseases”relationship.Objective:To explore the therapeutic effect of Compound Jinguo Weikang Powder on gastric cancer through differential expression analysis by generalized linear model and functional enrichment,and to provide basic research direction and clinical theoretical basis for the follow-up research on traditional Chinese medicine treatment of cancer.Methods The clinical information andRNA sequence data of gastric cancer patients were downloaded from TARGET database.The effective components and proteins ofActinidiaeChinensis Radix were retrieved from China National Knowledge Infrastructure(CNKI)and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the proteins of Compound Jinguo Weikang Powder were sorted out by Excel and R language.The data of gastric cancer patients derived from TARGET were sorted out for clustering analysis.R language Limmawas used for the differential analysis and functional enrichment was performed.Results Compound Jinguo Weikang Powder contains 1814 active components and 358 proteins.Samples of443 gastric cancer patients were retrieved from TARGET and 27226 genes were obtained from the expression profile.Some samples with incomplete data were excluded and finally the rest 407 samples were analyzed.Compound JinguoWeikangPowder andgastric cancer shared 352 target genes.According to theunivariate Cox analysis result of the 352 prognosis genes,patients with gastric cancer were classified

关 键 词：复方金果胃康散 TARGET Limma 功能富集 胃癌 GSEA 

分 类 号：R735.2[医药卫生—肿瘤]