| 陆文鹏,陈民,董小耘.基于GEO数据挖掘与网络药理学探讨小陷胸汤缓解NSCLC的分子靶点及作用机制[J].浙江中西医结合杂志,2022,32(5): |
| 基于GEO数据挖掘与网络药理学探讨小陷胸汤缓解NSCLC的分子靶点及作用机制 |
| Analysis of Mechanism and Molecular Targets of Xiaoxianxiong Decoction in the Treatment of NSCLC on Network Pharmacology and GEO Chip |
| 投稿时间：2021-08-25 修订日期：2021-10-19 |
| DOI： |
| 中文关键词: 小陷胸汤 非小细胞肺癌 网络药理学 作用机制 |
| 英文关键词: |
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| 中文摘要: |
| 目的：结合GEO数据挖掘利用网络药理学分析小陷胸汤缓解非小细胞肺癌(NSCLC)可能的作用机制。方法：利用GEO数据库下载NSCLC的相关GSE、GPL文件,用R软件进行差异基因分析,得到潜在疾病靶点；在TCMSP数据库中检索小陷胸汤中各组成药物的活性成分和分子靶点；取药物靶点基因与疾病差异基因交集,使用Cytoscape 3.8.2软件构建“药物-化合物-靶点”调控网络；在String数据库制作蛋白质-蛋白质相互作用(PPI)共表达网络；利用R软件进行基因本体(GO)和京都基因和基因组百科全书(KEGG)富集分析,探讨小陷胸汤治疗NSCLC的可能机制。结果：筛选共得到520个差异基因,在NSCLC疾病中表达上调有200个,表达下调320个,可作为诊断及治疗的潜在靶点。小陷胸汤中有效成分38种,对应的靶基因184个；PPI网络及Degree、Betweenness、Closeness算法拓扑分析结果显示MMP9、CAV1、MMP1、SPP1、CCL2、IGFBP3等6个靶点相互作用最强,可作为后续基础研究验证方向。GO、KEGG富集分析表明,小陷胸汤治疗缓解NSCLC主要涉及对类固醇、多细胞生物过程、丝氨酸型肽酶活性调节等方面,通过调节AGE-RAGE、p53、IL17、TNF等信号通路发挥治疗作用。结论：小陷胸汤缓解NSCLC具有多成分、多靶点、多通路的特点,其中主要成分为槲皮素、松柏苷、卡维丁等,主要作用靶点为MMP9、CCNB1、MMP1等,涉及主要通路涉及AGE-RAGE、p53、IL-17、TNF等。 |
| 英文摘要: |
| ［］ Objective: To explore the possible mechanism of Xiaoxianxion decoction in the treatment of non-small cell lung cancer(NSCLC) by GEO differential gene analysis and network pharmacology. Methods: The GSE and GPL files related to NSCLC were downloaded from GEO database,and the differential gene analysis was carried out in R software to obtain potential disease targets. The compound components and molecular targets of Xiaoxianxion decoction were searched by TCMSP database. The drug target genes and disease differential genes were intersected. The ″drug-compound-target″ regulatory network was constructed by Cytoscape Cytoscape 3.8.2 software. Protein-protein interaction (PPI) co-expression network was constructed in String database. Using R software to conduct enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to explore the possible mechanism of Xiaoxianxiong decoction in the treatment of NSCLC.Results: A total of 520 differential genes were screened, 200 of which were up-regulated in NSCLC diseases, and 320 were down-regulated in NSCLC diseases, which could be used as potential targets for diagnosis and treatment, and there were 38 active components and 184 active target in Xiaoxianxiong decoction. The topology analysis of PPI network and Degree, Betweenness, and Closeness algorithm showed that 6 targets such as MMP9, CAV1, MMP1, SPP1, CCL2 and IGFBP3 have the strongest interaction, which can be used as the verification direction of subsequent basic research. Go and KEGG enrichment analysis showed that response to steroid hormone, multi?multicellular organism process, serine?type peptidase activity and other aspects were mainly involved in the treatment of non-small cell lung cancer by Xiaoxianxiong decoction which played a therapeutic role by regulating age-rage, p53, IL17, TNF and other signaling pathways. Conclusion: Xiaoxianxiong treating NSCLC has the characteristics of multi-component, multi-target and multi-pathway . The main components are quercetin, coniferin and Carvetin, and the main targets are MMP9, CCNB1, MMP1, etc., and the main pathways involve age-rage, p53, IL-17, TNF and other pathways |
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