WGCNA分析筛选膝骨关节炎自噬相关基因
Screening for autophagy-related genes in knee osteoarthritis with bioinformatics
  
DOI:10.3969/j.issn.1006-7108.2024.04.009
中文关键词:  自噬相关基因  膝骨关节炎  生物信息学  富集分析  生物标志物
英文关键词:autophagy-related genes  knee osteoarthritis  bioinformatics  enrichment analysis  biomarker
基金项目:国家自然科学基金(81860401);内蒙古自治区科技厅重点项目(2022YFSH0075);内蒙古自治区硕士研究生科研创新项目(S20231189Z);内蒙古医科大学大学生科技创新项目
作者单位
赵连兴# 杜欣瑞# 刘凯 王建忠* 内蒙古医科大学第二附属医院内蒙古 呼和浩特 010030 
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中文摘要:
      目的 利用生物信息学分析方法筛选出膝骨关节炎中的差异性自噬相关基因,并获取其中特征性基因的miRNA及转录因子调控网络,进而阐释自噬在膝骨关节炎发病机制中的作用。方法 首先,通过GEO数据库下载并整合GSE55235和GSE169077的基因表达谱矩阵,随后使用R软件对整合后的基因表达矩阵分别进行差异分析、WGCNA分析。然后,将两种分析结果与从genecards数据库中获取的自噬相关基因取交集,得到差异性自噬相关基因,并对差异性自噬相关基因进行GO、KEGG、GSEA富集分析。最后,利用cytoscape中的CytoHubba插件筛选出特征性基因并在数据集GSE98918中对其进行验证。结果 经筛选后共得到了111个差异性自噬相关基因,经验证集验证最终得到7个可靠的特征性基因,分别是COL1A1、MMP9、CCL5、CX3CR1、ITGB2、PTPRC、CSF1R,并获得了特征基因的miRNA的调控网络和转录因子调控网络。结论 自噬在膝骨关节炎发病机制中具有重要作用,7个特征性自噬相关基因包括COL1A1、MMP9、CCL5、CX3CR1、ITGB2、PTPRC、CSF1R可作为潜在的生物标志物为诊断、治疗该疾病提供新思路。
英文摘要:
      Objective To screen out the differential autophagy-related genes in knee osteoarthritis by bioinformatics analysis, and to obtain the miRNA and transcription factor regulatory network of the hub genes, so as to illustrate the role of autophagy in the pathogenesis of knee osteoarthritis. Methods Firstly, the gene expression profiles of GSE55235 and GSE169077 were downloaded and integrated through the GEO database, and the difference analysis and WGCNA analysis of the integrated gene expression matrices were performed using the R package. Then, the two analysis results with the autophagy-related genes which obtained from the genecards database were intersected to obtain the differential autophagy-related genes, and the GO, KEGG, and GSEA enrichment analysis were performed in these genes. Finally, the hub genes were screened out by using CytoHubba plug-in in cytoscape and were validated in the validating dataset GSE98918. Results A total of 111 differentially expressed autophagy-related genes were obtained, in which 7 hub genes including COL1A1, MMP9, CCL5, CX3CR1, ITGB2, PTPRC, and CSF1R were considered more reliable. The regulatory networks of miRNA and transcription factor with the 7 hub genes were obtained respectively. Conclusion Autophagy plays an important role in the pathogenesis of knee osteoarthritis. Seven differentially expressed autophagy-related genes including COL1A1, MMP9, CCL5, CX3CR1, ITGB2, PTPRC, and CSF1R can be used as potential biomarkers to provide new ideas for the diagnosis and treatment of this disease.
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