基于生物信息学多数据库探讨半夏泻心汤干预胃癌细胞焦亡的分子机制

Study on molecular mechanism of Banxia Xiexin Decoction in intervention of gastric cancer cells pyroptosis based on multi database of bioinformatics

目的基于生物信息学多种数据库,探讨半夏泻心汤(BXXXD)干预胃癌(GC)细胞焦亡(pyroptosis)的分子机制,为胃癌患者生存、预后提供新思路。方法本研究使用到的生物信息学数据库包括中药系统药理学数据库与分析平台(Traditional TCMSP)、有机小分子生物活性数据(Pubchem)、String、人类基因的综合数据库(Genecard)、基因表达综合数据库(GEO)、癌症基因组图谱(TCGA)等。首先利用中药复方网络药理学方法获取"半夏泻心汤→胃癌→细胞焦亡"共有靶点并对其进行基因本体(GO)、京都基因与基因组百科全书(KEGG)分析;其次利用GEO数据库对胃癌芯片进行差异分析,绘制其差异表达基因(DEGs)火山图及热图,并利用韦恩图获取"半夏泻心汤→胃癌DEGs"共有靶点。通过TCGA数据库获取临床胃癌患者信息,比较正常组、胃癌组相关靶点的表达水平差异,并分析各靶点的表达水平与胃癌患者临床病理特征的关系。结果半夏泻心汤干预胃癌细胞焦亡共有29个靶点,多生物进程、多细胞组分、多分子功能、多条KEGG信号通路发挥作用,其中最主要的可能是:在细胞质中,分子靶点之间蛋白相互结合,通过神经活性配体-受体相互作用信号通路,正向调控转录途径的生物进程。进一步研究发现促胃泌素受体抗体(CCKBR)、ATPase H+/K+转运亚基Alpha(ATP4A)、ATPase H+/K+转运亚基Beta(ATP4B)为"半夏泻心汤→胃癌DEGs"的3个共有靶点。正常组与胃癌组分子靶点CCKBR、ATP4A、ATP4B的表达差异具有统计学意义(均P<0.05)。胃癌患者的CCKBR表达水平与年龄、T分期、M分期有关(均P<0.05),ATP4A表达水平与年龄、T分期有关(均P<0.05),ATP4B表达水平与组织学分期、T分期、N分期有关(均P<0.05)。结论利用生物信息学方法,通过多种数据库获取了半夏泻心汤干预胃癌细胞焦亡的相关靶点,并对该靶点与胃癌临床病理特征的关系进行了初步探讨,为中医药干预肿瘤疾病提供了新的研究方法。

Objective Based on a variety of bioinformatics databases,the molecular mechanism of Banxia Xiexin Decoction(BXXXD)in the intervention of gastric cancer cells pyroptosis was investigated,providing new ideas for the survival and prognosis of gastric cancer patients.Methods Bioinformatics databases used in this study include Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Pubchem,String,Genecard,Gene Expression Omnibus(GEO),and The Cancer Genome Atlas(TCGA),etc.Firstly,the common targets of"Banxia Xiexin Decoction→gastric cancer→pyroptosis"was obtained by the network pharmacology method of traditional Chinese medicine compound,and its Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were analyzed.Secondly,the difference of gastric cancer chip was analyzed by GEO database,and the differentially expressed genes(DEGs)volcano map and heat map were drawn.The common target of"Banxia Xiexin Decoction→Gastric cancer DEGs"was obtained by using Venn Diagram.The information of clinical gastric cancer patients was obtained through the TCGA database to compare the expression levels of relevant targets between the normal group and the gastric cancer group,and to analyze the relationship between the expression levels of each target and the clinicopathological characteristics of patients with gastric cancer.Results There were 29 targets of Banxia Xiexin Decoction in the intervention of gastric cancer cells pyroptosis,which play a role in multi-biological processes,multi-cellular components,multi-molecular functions and multiple KEGG signaling pathways.The most important may be that in the cytoplasm,proteins of molecular targets bind to each other and positively regulate the biological processes of transcription pathways through the neural active ligand-receptor interaction signaling pathway.Further study showed that cholecystokinin B receptor(CCKBR),ATPase H+/K+transporting subunit alpha(ATP4A),ATP4B were the three common targets of"Banxia Xiexin Decoction→gastric cancer DEGs".The expression of molecular targets CCKBR,ATP4A and ATP4B between normal group and gastric cancer group had statistical significance(all P<0.05).The expression level of CCKBR was correlated with age,T stage and M stage(all P<0.05),the expression level of ATP4A was correlated with age and T stage(all P<0.05),and the expression level of ATP4B was correlated with histological stage,T stage and N stage(all P<0.05).Conclusions By using bioinformatics method,the relevant targets of Banxia Xiexin Decoction in the intervention of gastric cancer cells pyroptosis were obtained through a variety of databases,and the relationship between the targets and the clinicopathological characteristics of gastric cancer was preliminatively discussed,which provided a new research method for the intervention of traditional Chinese medicine in tumor diseases.