基于WGCNA和分子对接分析干姜黄芩黄连人参汤干预胃腺癌的成分及靶点

Analysis of components and targets of Ganjiang Huangqin Huanglian Renshen Decoction in the treatment of gastric adenocarcinoma based on WGCNA and molecular docking

目的基于加权基因共表达网络分析(WGCNA)和分子对接研究干姜黄芩黄连人参汤干预胃腺癌的成分及靶点。方法从中药系统药理学数据库与分析平台中筛选与药物相关的成分和靶点,构建药物-化合物-靶标相互作用网络。在TCGA数据库下载胃腺癌基因表达数据,筛选与胃腺癌风险等级相关的关键模块,利用GO和KEGG数据库分析关键模块所包含基因的生物学功能。将模块基因上传到STRING数据库筛选关键靶点,通过分子对接技术对关键靶点进行半柔性对接反向验证。结果筛选得到59个活性成分,184个靶点,药物-化合物-靶点相互作用网络得到242个节点,676条边。通过WGCNA筛选出的关键模块共包括32个基因。GO和KEGG富集的结果主要涉及DNA完整性检验点、对金属离子的反应、p53信号通路、细胞周期和细胞衰老等。筛选得到的关键靶点为VEGFA、CDK1、CCND1。通过分子对接表明槲皮素、汉黄芩素、黄芩素等化合物与关键靶点结合活性较高。结论多种活性成分可以与胃腺癌的靶点相结合起到调节作用。

Objective To study the components and targets of Ganjiang Huangqin Huanglian Renshen Decoction in the treatment of gastric adenocarcinoma based on weighted gene co-expression network analysis(WGCNA)and molecular docking.Methods The drug-related components and targets were screened from the traditional Chinese medicine systems pharmacology database and analysis platform,and drug-compound-target interaction network was constructed.Gastric adenocarcinoma gene expression data were downloaded from TCGA database,and the key modules related to the risk level of gastric adenocarcinoma were screened.The biological functions of genes contained in the key modules were analyzed by GO and KEGG database.The module genes were uploaded to STRING database to screen key targets,and the semi-flexible docking reverse verification of key targets was carried out by molecular docking technology.Results Fifty-nine active components and 184 targets were screened,and 242 nodes and 676 edges were obtained from drug-compound-target interaction network.The key modules screened by WGCNA included 32 genes in total.The results of GO and KEGG enrichment mainly involve DNA integrity test points,reaction to metal ions,p53 signaling pathway,cell cycle,and cell senescence,etc.The key targets were VEGFA,CDK1,and CCND1.The molecular docking showed that quercetin,baicalein,baicalein,and other compounds had higher binding activities with key targets.Conclusion A variety of active ingredients can combine with the targets of gastric adenocarcinoma to play a regulatory role.