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目的 通过数据挖掘结合生物信息学技术，比较子宫腺肌病患者与正常人群的基因芯片数据库，查询差异基因，并分析差异基因参与的生物过程和潜在靶点，预测治疗子宫腺肌病的潜在药物。方法 利用基因表达数据库(GEO)筛选出GSE78851和GSE7307两个数据集，通过GEO2R分析芯片的共有差异基因，应用Omicshare制作差异基因热图，借助DAVID数据库对差异基因进行基因本体分析(GO)和京都基因与基因组百科全书(KEGG)分析，使用String构建蛋白质-蛋白质相互作用网络，筛选核心基因，再进一步利用Cytoscape 3.9.0的MCODE插件对差异表达基因进行模块分析。通过医学本体信息检索平台筛选治疗子宫腺肌病的中医药物。结果 筛选出433个共有差异基因，差异表达基因主要富集在细胞黏附、对雌二醇的反应、细胞凋亡等生物过程和氧化磷酸化、雌激素信号通路、PI3K-Akt等信号通路。共得出p53蛋白(TP53)、细胞色素C(CYCS)、肌动蛋白(ACTB)、Ⅳ型胶原酶(MMP2)、雌激素受体(ESR1)、CD44、丝裂原活化蛋白激酶3(MAPK3)、胰岛素样生长因子-Ⅰ(IGF-Ⅰ)、细胞质动力蛋白1重链1(DYNC1H1)、血小板反应蛋白-1(THBS1)、细胞色素氧化酶4Ⅱ(COX4Ⅱ)、NDUFAB1、人原纤维蛋白-1(FBN1)、ATP5A1、NDUFB7、ATP5G1等16个核心基因。在Cytoscape 3.9.0中进行模块分析并得出两个重要模块，对其进行分析后发现模块1基因主要与氧化磷酸化信号通路相关，模块2基因主要与Rap1、Wnt信号通路相关。筛选得到丹参、当归、茯苓、三七、厚朴花、茶树根、蚕砂7味出现频次最高的中药。结论 通过差异表达基因和富集分析得到的生物过程与信号通路可以为子宫腺肌病的潜在治疗靶点提供参考，通过核心基因映射得到了治疗子宫腺肌病的潜在药物，为子宫腺肌病的治疗提供新的思路。
Abstract：Objective:By combining data mining with bioinformatics technology, the gene chip databases of adenomyosis patients and normal people were compared, the differential genes were searched, then the biological processes and potential targets involved in the differential genes were analyzed to predict the potential drugs.Methods:The GEO database was used to screen out the two data sets of GSE78851 and GSE7307,GEO2R was used to analyze the common differential genes of the chip, the differential gene heat map was generated by Omicshare. The GO and KEGG analysis of differential genes was performed by DAVID database, and the protein-protein interaction network was constructed by using String. The core gene was further subjected to modular analysis of differentially expressed genes using the MCODE plugin of Cytoscape 3.9.0. The drug for the treatment of adenomyosis was screened by the medical ontology information retrieval platform.Results:A total of 433 consensus differential genes were screened. The differentially expressed genes were mainly enriched in cell adhesion, estradiol response, apoptosis and other biological processes and oxidative phosphorylation, estrogen signaling pathway, PI3K-Akt and other signaling pathways. A total of 16 core genes were found, including P53 protein(TP53),cytochrome C(CYCS),actin(ACTB),type Ⅳ collagenase(MMP2),estrogen receptor(ESR1),CD44,mitogen-activated protein kinase 3(MAPK3),insulin-like growth factor I(IGF-1),cytoplasmic dynein 1 heavy chain 1(DYNC1H1),thrombospondin-1(THBS1),cytochrome oxidase 4Ⅱ(COX4Ⅱ),NDUFAB1,human fibrillin-1(FBN1),ATP5A1,NDUFB7,and ATP5G1. The module analysis was carried out in Cytoscape 3.9.0 and two important modules were obtained, and it was found that the module 1 gene was mainly related to the oxidative phosphorylation signaling pathway, and the module 2 gene was mainly related to the Rap1 and Wnt signaling pathways. The traditional Chinese medicines such as Salvia miltiorrhiza, Angelica, Poria, Sanqi, Magnolia, Camellia, and Silkworm were screened.Conclusions:The biological processes and signal pathways obtained by differentially expressed genes and enrichment analysis can provide a reference for potential targets of adenomyosis treatment. The potential drugs for adenomyosis are obtained through core gene mapping, which would provide new ideas for the treatment of adenomyosis.
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基本信息:
中图分类号:R711.71;Q811.4
引用信息:
[1]杨书彬,练晓梅,师伟,等.基于生物信息学方法的子宫腺肌病关键靶点与中药筛选研究[J].生殖医学杂志,2024,33(02):216-228.
基金信息:
中央级公益性科研院所基本科研业务费专项资金(ZZ2019003,XTCX2021003); 国家自然科学基金(81873330); 山东省重大科技创新工程项目(2018CXGC1309)
2023-06-25
2023
2023-09-05
2024-01-12
2024
1
2024-02-15
2024-02-15