血清无细胞RNA铁死亡相关基因预测早发型子痫前期的初步研究

Prediction of early preeclampsia with ferroptosis-related genes in plasma cell-free RNA

目的鉴定早发型子痫前期中具有诊断意义的新型铁死亡相关基因。方法首先从FerrDb数据库中获取258个铁死亡相关基因,从基因表达综合数据库中获取早发型子痫前期患者的血清无细胞RNA基因表达谱和临床信息。此外,通过线性模型微阵列数据分析筛选出差异表达基因,结合韦恩图得到与铁死亡相关的基因表达谱。本研究对这些铁死亡相关基因进行了功能富集分析,进一步将获得的铁死亡相关基因采用LASSO方法构建早发型子痫前期相关特征的模型,确定一些在早发型子痫前期诊断中关键的铁死亡相关基因。结果首先,通过线性模型微阵列数据分析获得早发型子痫前期差异表达基因共4011个,其中上调基因2774个,下调基因1237个;其次,获得了37个与铁死亡相关的差异表达基因,涉及程序性细胞死亡、细胞凋亡、自噬、程序性死亡-配体1表达和铁死亡信号通路;再次,经过多变量生存分析,整合了胎龄、子痫前期状态和37个与铁死亡相关的差异表达基因,成功构建了LASSO诊断模型;最终发现了15个铁死亡相关基因(IFNG、AKR1C1、CAV1、SLC1A4、ENPP2、ACVR1B、ULK1、ZNF419、BID、XBP1、GPX4、MAPK14、WIPI1、DPP4、SLC7A5),成为诊断早发型子痫前期的关键基因;最后,成功构建了早发型子痫前期的15个铁死亡相关基因相关的蛋白质-蛋白质相互作用网络。结论血清无细胞RNA中的15个铁死亡相关基因与早发型子痫前期存在相关性,未来需要进一步验证其在早发型子痫前期诊断的价值。

Objective To identify novel ferroptosis-associated genes with diagnostic significance in early-onset preeclampsia.Methods First,we obtained 258 ferroptosis-related genes from the FerrDb database,and the plasma cell-free RNA gene expression profiles and clinical information of patients with early preeclampsia from the GEO database.In addition,the differentially expressed genes were screened out by LIMMA analysis,combined with the Venn diagram to obtain the gene expression profile related to Ferroptosis.Then,we performed a functional enrichment analysis of these ferroptosis-related genes.Further use the obtained ferroptosis-related genes for LASSO to construct a model of early preeclampsia-related features,and determine some key ferroptosis-related genes in the diagnosis of early preeclampsia.Results First,4011 differentially expressed genes in early preeclampsia were obtained by LIMMA analysis,of which 2774 genes were up-regulated and 1237 genes were down-regulated.Secondly,37 differentially expressed genes related to ferroptosis were obtained,which were involved in programmed cell death,apoptosis,Autophagy,PD-L1 expression,and Ferroptosis signaling pathways.Third,after multivariate survival analysis,we integrated gestational age,preeclampsia status and 37 differentially expressed genes related to ferroptosis,and successfully constructed a LASSO diagnostic model.Finally,15 ferroptosis-related genes(IFNG,AKR1C1,CAV1,SLC1A4,ENPP2,ACVR1B,ULK1,ZNF419,BID,XBP1,GPX4,MAPK14,WIPI1,DPP4,and SLC7A5)were discovered,which became the key genes for the diagnosis of early preeclampsia.Fourth,a protein-protein interaction network related to 15 ferroptosis-related genes was successfully constructed.Conclusions The 15 ferroptosis-related genes in plasma cell-free RNA have significant diagnostic value for early preeclampsia and are expected to be potential therapeutic targets for early preeclampsia.