基于生物信息学和网络药理学筛选胃癌关键基因及中药活性成分研究  

Identification of key genes of gastric cancer and active components of traditional Chinese medicine based on bioinformatics and network pharmacology

作　　者：陈丽凤[1] 陈默 吴昦辰 陈一斌[1] 郑启忠[1] 张冬英[1] CHEN Lifeng;CHEN Mo;WU Haochen;CHEN Yibin;ZHENG Qizhong;ZHANG Dongying

机构地区：[1]厦门市中医院,福建厦门361015

出　　处：《中医临床研究》2024年第24期72-79,共8页Clinical Journal Of Chinese Medicine

基　　金：厦门市中医院院内课题资助项目(XMSZYY202004);吴耀南全国名老中医药专家传承工作室专项资金(国中医药人教函〔2022〕75号);第七批全国老中医药专家学术经验继承工作专项资金(国中医药人教函〔2022〕76号)。

摘　　要：目的:本研究旨在利用生物信息学方法探索驱动胃癌进展的关键基因,并结合网络药理学分析筛选潜在的中药活性成分,以期为预防和治疗胃癌提供依据。方法:从NCBI的GEO数据库下载基因表达谱芯片(GSE191275),利用GEO2R筛选出胃癌实验组VS肠上皮化生组,肠上皮化生VS非萎缩性胃炎的差异表达基因(Differentially Exprsssed Gense,DEGs),并使用维恩图搜索“非萎缩性胃炎-肠上皮化生-胃癌”进程中变化规律一致的基因。通过STRING数据库构建蛋白质的相互作用网络,用CytoScape来筛选出关键基因。采用ROC曲线分析进一步筛选胃癌治疗的潜在靶点。从中药系统药理学数据库与分析平台(TCMSP)挖掘潜在中药活性成分。临床纳入厦门市中医院脾胃科门诊收治的40例胃癌前病变患者作为研究对象,按随机数字表法将患者分为常规对照组和槲皮素补充组各20例。观察两组患者治疗效果、血清学指标、靶点抑制以及不良反应情况。结果:在胃癌病程中共鉴定出49个持续上调和39个持续下调的基因。通过双重筛选和鉴别确定了前蛋白转化酶枯草溶菌素1(Recombinant Proprotein Convertase Subtilisin/Kexin Type 1,PCSK1)、前列腺素氧化环化酶(Prostaglandin-endoperoxide Synthase,PTGS)2、基质金属蛋白酶(Matrix Metallopeptidase,MMP)3和C-C基序趋化因子(C-C Motif Chemokine,CCL)20作为预防和治疗胃癌的潜在基因靶点。从TCMSP挖掘靶向基因靶点的潜在中药活性成分,经过多项筛选规则鉴别出槲皮素为PTGS2/MMP3双重抑制剂。通过临床观察证实槲皮素补充显著提高了常规治疗的总有效率,差异有统计学意义(P<0.05)。同时槲皮素补充还显著下调了血清胃黏膜环氧合酶(Cyclooxygenase,COX)-2、p53水平和胃黏膜的PTGS2和MMP3 mRNA表达(P<0.05)。两组不良反应发生率的差异无统计学意义(P>0.05)。结论:本研究认为PCSK1、PTGS2、MMP3和CCL20是“非萎缩性胃炎-肠上皮�Objective:This study aims to explore key genes that drive the progression of gastric cancer through bioinformatics,and screening potential active ingredients of traditional Chinese medicine combined with network pharmacological analysis,with a prospect of providing basis for the prevention and treatment of gastric cancer.Methods:The gene expression profile chip(GSE191275)was downloaded from the GEO database of NCBI,and the differentially expressed genes(DEGs)of gastric cancer experimental group VS intestinal metaplasia group and intestinal metaplasia VS non-atrophic gastritis were screened by GEO2R,and the genes with the same change pattern in the process of“non-atrophic gastritis-intestinal metaplasia-gastric cancer”were searched by Venn diagram.The interaction network of proteins was constructed by STRING database,and key genes were screened by CytoScape.ROC curve analysis was used to further screen potential targets for gastric cancer treatment.Potential active ingredients of Chinese medicine were extracted from TCMSP.A total of 40 patients with gastric cancer prelesions admitted to the Outpatient Department of Spleen and Stomach,Xiamen Hospital of Traditional Chinese Medicine were included as the study subjects,and the patients were divided into the routine control group and the quercetin supplement group according to random number table method,with 20 cases in each group.The therapeutic effect,serological indexes,target inhibition and adverse reactions in the two groups were observed.Results:A total of 49 continuously up-regulated and 39 continuously down-regulated genes during the course of gastric cancer were identified.Through double screening and identification,PCSK1,PTGS2,MMP3 and CCL20 were identified as potential gene targets for the prevention and treatment of gastric cancer.Quercetin was identified as a dual inhibitor of PTGS2/MMP3 after a number of screening rules for potential TCM active ingredients targeted by TCMSP.The clinical observation confirmed that quercetin supplementation significant

关 键 词：胃癌 生物信息学 关键基因 网络药理学 中药活性成分 

分 类 号：R273[医药卫生—中西医结合]