摘要
目的探讨黄芪治疗胃癌的作用机制。方法通过中药系统药理学数据库和分析平台检索黄芪的化学成分及作用靶点。癌症基因组图谱数据库下载胃癌基因表达谱及临床特征数据,采用加权基因共表达网络分析(weighted correlation network analysis,WGCNA)识别胃癌共表达模块。将黄芪的作用靶点与胃癌共表达模块、差异基因取交集。STRING数据库构建蛋白质–蛋白质相互作用(protein-protein interaction,PPI)网络并提取黄芪改善胃癌预后的潜在靶点。通过GSE54129数据集、人类蛋白质图谱数据库、分子对接对潜在靶点进行验证。结果共检索到黄芪有效活性成分16个及对应靶点190个;筛选得到差异表达基因2694个,其中上调基因1124个,下调基因1570个;构建的WGCNA共表达网络发现青绿色模块与胃癌有显著而稳定的相关性,构建韦恩图得到黄芪改善胃癌预后的27个差异表达基因。PPI网络鉴定得到10个关键基因,其中,微囊蛋白1(caveolin 1,CAV1)、前列腺素E2受体EP3亚型(prostaglandin E2 receptor EP3 subtype,PTGER3)与胃癌患者的生存显著相关。分子对接结果发现,黄芪活性成分与PTGER3具有较好的结合能。结论黄芪改善胃癌预后的作用机制可能与调节CAV1和PTGER3有关。
Objective To explore the mechanism of astragalus in treatment of gastric cancer.Methods The chemical constituents and targets of astragalus were searched through traditional Chinese medicine systems pharmacology database and analysis platform.The Cancer Genome Atlas database was downloaded for gastric cancer gene expression data and clinical data,and weighted correlation network analysis(WGCNA)was used to identify gastric cancer co-expression modules.The target of astragalus was intersected with gastric cancer co-expression modules and differential genes.Potential targets were validated using the GSE54129 dataset,Human Protein Atlas database,and molecular docking.Results A total of 16 active ingredients and 190 corresponding targets of astragalus were retrieved.2694 differentially expressed genes were screened,of which 1124 genes were up-regulated and 1570 genes were down-regulated.The constructed WGCNA co-expression network showed a significant and stable correlation between the cyan module and gastric cancer,and 27 differentially expressed genes of astragalus were obtained by constructing the Venn diagram.Ten key genes were identified by PPI network,among which caveolin 1(CAV1)and prostaglandin E2 receptor EP3 subtype(PTGER3)were significantly correlated with the survival of patients with gastric cancer.The molecular docking results showed that the active ingredients of astragalus had good binding energy with PTGER3.Conclusion The mechanism of astragalus improving the prognosis of gastric cancer may be related to regulating CAV1 and PTGER31.
作者
胡文杰
王钰婷
于白莉
HU Wenjie;WANG Yuting;YU Baili(Department of General Practice,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu,610075,Sichuan,China)
出处
《中国现代医生》
2023年第16期80-85,共6页
China Modern Doctor
关键词
黄芪
加权基因共表达网络分析
胃癌
生存分析
生物信息
Astragalus
Weighted correlation network analysis
Gastric cancer
Survival analysis
Bioinformatics