【摘要】 目的 本文旨在通过网络药理学和在线生物学分析，探究E7766治疗膀胱癌的作用靶点以及作用机制。方法 借助多个药物与疾病数据库，获得E7766和膀胱癌的相关靶点。利用Cytoscape软件，确定E7766治疗膀胱癌的核心靶点。通过David数据库对筛选出的靶点进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)富集通路分析。运用基因表达谱交互分析(GEPIA)数据库分析核心靶点在膀胱癌中的表达以及与患者预后的关系。用肿瘤免疫评估资源(TIMER)数据库对核心靶点基因进行免疫浸润分析。结果 获取了药物-疾病核心基因靶点：胱天蛋白酶3(CASP3)、基质金属蛋白酶9(MMP9)、西罗莫司靶蛋白(mTOR)、前列腺素内过氧化物合酶2(PTGS2)、丝裂原活化蛋白激酶1(MAPK1)。KEGG富集分析结果表明细胞凋亡通路、肿瘤坏死因子(TNF)信号通路等多个通路对膀胱癌产生治疗作用。GEPIA数据库分析发现MMP9在膀胱癌组织中高表达，PTGS2低表达，差异有统计学意义(P<0.05);MAPK1表达水平与预后呈负相关，MAPK表达越低，患者的预后越好(P<0.05)。TIMER肿瘤免疫数据库发现了核心靶点与多种免疫细胞的浸润水平密切相关，在树突细胞和CD8~+T细胞的浸润中起重要作用。结论 E7766通过CASP3、MMP9、mTOR、PTGS2、MAPK1等多个靶点及细胞凋亡、TNF信号通路等多条通路影响膀胱癌细胞的凋亡、炎症等生物学过程。更多还原

【Abstract】 Objective This article aims to explore the target and mechanism of E7766 in the treatment of bladder cancer through network pharmacology and online biological analysis. Methods Relevant targets of E7766 and bladder cancer were obtained with the help of multiple drug and disease databases. The core target of E7766 in the treatment of bladder cancer was determined by using Cytoscape software. Perform gene ontology(GO) analysis and Kyoto encyclopedia of genes and genomes(KEGG) enrichment pathway analysis on the selected targets through the David database. The Gene Expression Profiling Interactive Analysis(GEPIA) database was used to analyze the expression of core targets in bladder cancer and their relationship with patient prognosis. Perform immune infiltration analysis on core target genes using the Tumor Immune Estimation Resource(TIMER) database. Results Obtained drug disease core gene targets: caspase-3(CASP3), matrix metalloproteinase-9( MMP9),mammalian target of rapamycin( mT OR),prostaglandin endoperoxide synthase 2( PTGS2) and mitogen activated protein kinase 1( MAPK1). KEGG enrichment analysis showed that multiple pathways such as apoptosis pathway and tumor necrosis factor( TNF) signaling pathway had therapeutic effects on bladder cancer. GEPIA database analysis showed that MMP9 was highly expressed in bladder cancer tissues,while PTGS2 was low( P < 0. 05); the expression level of MAPK1 is negatively correlated with prognosis,and the lower the expression of MAPK,the better the prognosis of patients( P < 0. 05). The TIMER tumor immune database has found that core targets are closely related to the infiltration levels of various immune cells,playing an important role in the infiltration of dendritic cells and CD8+T cells. Conclusion E7766 influences biological processes such as apoptosis and inflammation of bladder cancer cells through multiple targets such as CASP3,MMP9,mT OR,PTGS2,MAPK1 and multiple pathways such as apoptosis and TNF signaling pathway.更多还原