复方川芎嗪抗胃癌的网络药理学研究

Network Pharmacology Study of Compound Ligustrazine in Gastric Cancer Therapy

目的利用网络药理学,结合基因功能注释及临床数据分析,探索复方川芎嗪在胃癌中的潜在作用位点以及机制。方法首先利用SwissTargetPrediction数据库筛选复方川芎嗪的潜在药物作用位点,并结合OMIM和Genecard数据库获取胃癌相关靶点。通过交集分析确定潜在的治疗靶点。随后,利用ClusterProfiler的方法对交集下游靶点进行功能注释。同时,利用TCGA数据库获取胃癌患者的原始数据,进行免疫浸润分析、miRNA分析、关键基因的转录调控分析、基因集富集分析(gene set enrichment analysis,GSEA)、基因集差异分析(gene set variation analysis,GSVA)、nomogram模型构建以及全基因组关联研究(genome-wide association studies,GWAS)分析等。结果通过网络药理学筛选,共发现川芎嗪作用于胃癌有14个潜在治疗靶点。功能注释结果显示,这些靶点主要涉及激素代谢、药物代谢和信号转导等通路。基于log rank检验,关键基因ELANE和MPO的表达在胃癌生存曲线的比较中,差异有统计学意义(P<0.05),并与免疫细胞浸润密切相关。此外,GSEA和GSVA结果提示,ELANE和MPO可能通过多条信号通路影响胃癌的发展。结论本研究通过综合多种分析方法,揭示了复方川芎嗪可能通过调节潜在靶点ELANE和MPO,以及相关的信号通路,对胃癌起治疗作用。

Objective To explore the potential role and mechanism of compound tetramethylpyrazine in gastric cancer therapy by using network pharmacology analysis combined with gene function annotation and clinical data analysis.Methods SwissTargetPrediction database was used to screen the potential drug action sites of compound tetramethylpyrazine,and the OMIM and Genecard databases were used in combination to obtain gastric cancer-related targets.Intersection analysis was performed to identify potential therapeutic targets.Subsequently,the method of ClusterProfiler was used to perform functional annotation of the downstream targets of intersection.In addition,The Cancer Genome Atlas(TCGA)database was used to obtain the original data of gastric cancer patients,and the immune infiltration analysis,miRNA analysis,transcriptional regulation analysis of key genes,gene set enrichment analysis(GSEA),gene set variation analysis(GSVA),nomogram model construction,and genome-wide association studies(GWAS)were performed.Results Through network pharmacological screening,we found 14 potential therapeutic targets through which tetramethylpyrazine acted on gastric cancer.Functional annotation showed that these targets were mainly involved in the pathways for hormone metabolism,drug metabolism,and signal transduction.Based on log rank test,the expression of the key genes,ELANE and MPO,showed significant difference in the comparison of gastric cancer survival curves(P<0.05),and were closely associated with immune cell infiltration.In addition,GSEA and GSVA results suggested that ELANE and MPO might influence the development of gastric cancer through multiple signaling pathways.Conclusion In this study,by using multiple analysis methods in an integrated way,we found that ligustrazine may have therapeutic effects on gastric cancer by regulating the potential targets of ELANE and MPO,as well as the relevant signaling pathways.