子宫内膜异位症铁死亡相关诊断基因及治疗靶点的遗传分析  

Genetic analysis of potential biomarkers and therapeutic targets in ferroptosis from endometriosis

作　　者：路畅[1] 谢成茂 魏薇[1] Lu Chang;Xie Chengmao;Wei Wei(Department of Gynecology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing Maternal and Child Health Care Hospital,Beijing 100026)

机构地区：[1]首都医科大学附属北京妇产医院/北京妇幼保健院妇科,北京100026

出　　处：《现代妇产科进展》2023年第3期188-195,共8页Progress in Obstetrics and Gynecology

摘　　要：目的:通过生物信息学方法分析子宫内膜异位症(EMs)铁死亡相关诊断基因及治疗靶点。方法:从GEO及FerrDb数据库下载EMs相关基因芯片数据和铁死亡相关基因信息;通过LASSO算法及SVM-RFE算法筛选EMs铁死亡相关诊断基因,并分析这些基因的诊断能力;应用R软件对筛选出的诊断基因进行功能、通路、GSEA富集分析及GSVA富集分析;通过DGIdb数据库检索与诊断性基因相关的药物,并基于诊断基因构建ceRNA网络。应用CIBERSORT分析诊断基因与免疫细胞之间的相关性。结果:获得31个EMs铁死亡相关差异基因,通过LASSO算法及SVM-RFE算法筛选出8个EMs铁死亡相关的诊断基因,包括DUOX2、SLC38A1、MAPK1、PANX1、HSPB1、JUN、P4HB及PDK4,并证明了这些基因具有可靠的诊断能力。功能富集分析表明,这些诊断基因可能通过参与自噬、免疫细胞、细胞因子和多种激酶的调节等,在EMs的发病机制中发挥着重要的作用。通过DGIdb数据库检索到245种与8个诊断性基因相关的药物,而基于诊断基因构建的ceRNA网络揭示了这些基因之间存在着复杂的调控关系。CIBERSORT分析表明,EMs免疫微环境的变化可能与SLC38A1及P4HB密切相关。结论:本研究挖掘了EMs的铁死亡相关诊断基因及其治疗靶点,为研究EMs的分子机制、临床诊断和治疗提供了新的研究方向及理论基础。Objective:Analysis of diagnostic genes and therapeutic targets related to ferroptosis in endometriosis(EMs)by bioinformatics.Methods:We downloaded EMs related gene chip data and ferroptosis related gene information from GEO and FerrDb databases.LASSO algorithm and SVM-RFE algorithm were used to screen the diagnostic genes related to ferroptosis in EMs,and then analyzed the diagnostic ability of these genes.R software was used to analyze the function,pathway,GSEA enrichment and GSVA enrichment of the selected diagnostic genes.In addition,we searched the drugs related to diagnostic genes through the DGIdb database,and constructed the ceRNA network based on the diagnostic genes.Finally,we used CIBERSORT to analyze the correlation between diagnostic genes and immune cells.Results:First,we obtained 31 EMs ferroptosis related differential genes,and then screened 8 EMs ferroptosis related diagnostic genes through LASSO algorithm and SVM-RFE algorithm,including DUOX2,SLC38A1,MAPK1,PANX1,HSPB1,JUN,P4HB and PDK4,and proved that these genes have reliable diagnostic ability.Functional enrichment analysis showed that these diagnostic genes may play an important role in the pathogenesis of EMs by participating in the regulation of autophagy,immune cells,cytokines and various kinases.In addition,we searched 245 drugs related to 8 diagnostic genes through the DGIdb database,and the ceRNA network constructed based on diagnostic genes revealed the complex regulatory relationship between these genes.CIBERSORT analysis showed that the changes of immune microenvironment of EMs may be closely related to SLC38A1 and P4HB.Conclusion:This study explored the ferroptosis related diagnostic genes and therapeutic targets of EMs,providing a new research direction and theoretical basis for the study of the molecular mechanism,clinical diagnosis and treatment of EMs.

关 键 词：子宫内膜异位症 铁死亡 生物信息学 诊断基因 免疫微环境 

分 类 号：R711.71[医药卫生—妇产科学]