通过生物信息学分析鉴定糖尿病视网膜病变的关键生物标志物和免疫浸润  

Identification of key biomarkers and immune infiltration of fibrovascular membranes in diabetic retinopathy patients by bioinformatics analysis

作　　者：王珍 廖敏 覃方鳞 郝亚荣[1] WANG Zhen;LIAO Min;QIN Fanglin;HAO Yarong(Department of Geriatric,Wuhan University People's Hospital,Wuhan 430000,China)

机构地区：[1]武汉大学人民医院老年病科,武汉430000

出　　处：《中国免疫学杂志》2024年第9期1925-1932,共8页Chinese Journal of Immunology

基　　金：湖北省自然科学基金项目(2016CFB6673)。

摘　　要：目的:通过生物信息学方法为糖尿病视网膜病变中的相关机制提供理论依据。方法:通过GEO数据库筛选出增殖性糖尿病视网膜病变(PDR)数据集GSE60439和GSE94019。使用R语言提取GSE60439数据集中的表达数据进行t检验,筛选出差异基因,筛选条件为P<0.05和|log2FC|≥1;采用WGCNA选择GSE94019数据集中与PDR相关的重要模块;对差异基因及重要模块中的基因取交集得到关键基因。对关键基因进行GO及KEGG富集分析;构建PPI网络鉴定出高风险关键蛋白。最后,使用CIBERSORTx分析免疫细胞在PDR中的浸润,采用Pearson相关性检验分析免疫细胞与关键基因的相关性。结果:最终筛选出3个核心基因,即Col1a1、Col1a2、Col3a1,其表达与M2巨噬细胞呈正相关,且核心基因富集于AGEs-RAGE信号通路。结论:正反馈可能存在于M2巨噬细胞、AGEs-RAGE信号通路及胶原基因(Col1a1、Col1a2、Col3a1)之间,即使没有高糖的刺激,这种恶性循环仍可能持续损害视网膜组织。Objective:To provide theoretical basis for the relevant mechanisms in diabetic retinopathy by bioinformatics methods.Methods:Proliferative diabetic retinopathy(PDR)datasets GSE60439 and GSE94019 were screened through GEO database.Expression data of GSE60439 dataset was extracted using R language,and the differential genes were determined,with the screening conditions of P<0.05 and|log2FC|≥1;WGCNA was used to select the important modules related to PDR in GSE94019 dataset;key genes were obtained by intersecting differential genes and genes in important modules.Key genes were subjected to GO and KEGG enrichment analysis;PPI network was constructed to identify high-risk key proteins.Finally,CIBERSORTx was used to analyze the infiltration of immune cells in PDR,and Pearson correlation analysis was used to screen key genes related to immune cells as core genes.Results:Three core genes were finally obtained,namely Col1a1,Col1a2 and Col3a1,their expressions were positively correlated with M2 macrophages,and the core genes were enriched in the AGEs-RAGE signaling pathway.Conclusion:Positive feedback may be formed between M2 macrophages,AGEs-RAGE signaling pathway and collagen genes(Col1a1,Col1a2,Col3a1),even without the stimulation of high glucose,this vicious circle may continue to damage retinal tissue.

关 键 词：糖尿病视网膜病变 纤维血管膜 AGEs-RAGE信号通路 M2巨噬细胞 胶原基因 

分 类 号：R774.1[医药卫生—眼科]