Xu Wei, Deng Zhaomin, Wang Xin, Jiang Hao
（ 610041） Department of Gastroenterology and Hepatology, Laboratory for Aging and Cancer Research, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics ,State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 Sep 20;55(5):1114-1122. doi: 10.12182/20240960503.
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.
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.
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, and , showed significant difference in the comparison of gastric cancer survival curves (<0.05), and were closely associated with immune cell infiltration. In addition, GSEA and GSVA results suggested that and might influence the development of gastric cancer through multiple signaling pathways.
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 and , as well as the relevant signaling pathways.
通过网络药理学分析结合基因功能注释和临床数据分析，探讨复方川芎嗪在胃癌治疗中的潜在作用及机制。
利用瑞士靶点预测数据库筛选复方川芎嗪的潜在药物作用位点，并结合OMIM和基因卡数据库获取胃癌相关靶点。进行交集分析以确定潜在治疗靶点。随后，采用ClusterProfiler方法对交集下游靶点进行功能注释。此外，利用癌症基因组图谱（TCGA）数据库获取胃癌患者的原始数据，并进行免疫浸润分析、miRNA分析、关键基因的转录调控分析、基因集富集分析（GSEA）、基因集变异分析（GSVA）、列线图模型构建和全基因组关联研究（GWAS）。
通过网络药理学筛选，我们发现了14个川芎嗪作用于胃癌的潜在治疗靶点。功能注释表明，这些靶点主要参与激素代谢、药物代谢和信号转导途径。基于对数秩检验，关键基因 和 在胃癌生存曲线比较中表达有显著差异（<0.05），且与免疫细胞浸润密切相关。此外，GSEA和GSVA结果表明， 和 可能通过多种信号通路影响胃癌的发生发展。
本研究通过综合运用多种分析方法，发现川芎嗪可能通过调节 和 的潜在靶点以及相关信号通路对胃癌具有治疗作用。
