泡型包虫病中与细胞焦亡相关基因的鉴定及其免疫微环境分析

Identification of pyroptosis-related genes and analysis of immune microenvironment in alveolar echinococcosis

目的 通过生物信息学方法筛选泡型包虫病中与细胞焦亡相关的基因,并探讨这些焦亡基因对免疫微环境的影响。方法 从基因表达综合数据库(Gene Expression Omnibus,GEO)获取泡型肝包虫组织的基因表达谱。使用R统计分析软件和与筛选相关的R软件编译包对泡型包虫病中与焦亡相关的基因进行筛选,并做功能富集分析及诊断性预测。使用STRING在线数据库、NetworkAnalyst数据库分析相关焦亡基因蛋白-蛋白、靶基因-miRNA、靶基因-转录因子、靶基因-药物的相关互作网络。绘制ROC曲线比较曲线下面积来评估预测基因的诊断能力。使用ssGSEA算法分别评估泡型包虫病和焦亡相关基因与免疫细胞浸润水平的关系。结果 鉴定出25个基因为AE-PRGs的关键基因。通过基因本体论分析和通路富集分析、单样本变异富集分析,发现这25个关键基因主要富集的通路包括先天性免疫反应的调节和激活通路和Toll受体信号通路、TNF信号通路、NOD受体信号通路等。此外,通过免疫浸润分析发现,焦亡相关基因与多种免疫细胞密切相关。结论 CEBPB、CHMP2B、NCR1和POP1可能是与泡型包虫病发生、发展相关的关键基因,并发现泡型包虫病中细胞的过度焦亡不利于免疫微环境,这为泡型包虫病的诊断和治疗提供了新的视角。

Objective To screen the genes related to pyroptosis in alveolar echinococcosis by bioinformatics method,and to explore the effect of these pyroptosis genes on immune microenvironment.Methods Get the gene expression profiling of alveolar echinococcosis(AE)liver tissue from gene expression omnibus(GEO).Use R statistical analysis software and related R packets to screen related pyroptosis genes in alveolar echinococcosis,and the functional enrichment analysis and diagnostic prediction were performed.String online database and NetworkAnalyst database were used to analyze the correlation network analysis of pyroptosis-related genes protein-protein,Target gene-miRNA,Target gene-transcription factor and Target gene-drug.ROC curves were plotted and areas under the curves were compared to assess the diagnostic ability of predictive genes.The relationship between AE and AE-PRGs immune cell infiltration was evaluated by ssGSEA algorithm.Results Twenty-five genes were identified as key genes of AE-PRGs.Through Gene Ontology Analysis,pathway enrichment analysis and single-sample variation enrichment analysis,it was found that the 25 key genes were mainly enriched in innate immune response,Toll receptor signaling pathway,TNF signaling pathway,NOD receptor signaling pathway and so on.In addition,the genes related to PRGs were closely related to many kinds of immune cells in immune infiltration analysis.Conclusion CEBPB,CHMP2 B,NCR1 and POP1 may be the key genes related to the occurrence and development of alveolar echinococcosis.It was found that the excessive cell pyroptosis in alveolar echinococcosis is unfavorable to the immune microenvironment,this provide a new perspective for the diagnosis and treatment of alveolar echinococcosis.