Meta-analysis And Bioinformatics Analysis Of The Diagnostic Value Of Blood MiRNAs In Neonatal Hypoxic-ischemic Encephalopathy

Objective:The diagnostic biomarkers of neonatal hypoxic-ischemic encephalopathy are particularly important for guiding and optimizing treatment.Mi RNAs(micro RNAs)have attracted much attention because of their diagnostic value in various brain injuries.This study uses meta-analysis and bioinformatics methods to explore the diagnostic performance and potential molecular mechanism of circulating mi RNAs in neonatal HIE,and to explore the biological processes,signal pathways and ce RNA regulatory network network that these mi RNAs may participate in in neonatal HIE,so as to provide the basis and ideas for further exploration of basic scientific research and clinical application.。Methods:1.This study summarizes all relevant studies to determine the potential diagnostic value of mi RNAs in neonatal HIE.This study included the article on the use of mi RNAs in the diagnosis of HIE children updated to August 1,2022.The sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,diagnostic odds ratio(DOR)and area under curve(AUC)were summarized using a random effect model.Meta regression and subgroup analysis were used to explore the source of heterogeneity,and the Deek’s funnel map was used to assess whether there was publication bias.2.The GEO data set GSE12178 of blood samples from newborns with HIE was analyzed for differential expression,and the target genes of mi RNAs and their biological functions and signal pathways were identified and explored using ENCORI,mi Rstarbase and other databases.The STRING platform was used to analyze the protein-protein interaction of the target genes,and the circ RNA-mi RNA-m RNA(transcription factor)regulatory network was constructed using the Circ Bank database.Results:1.The overall sensitivity,specificity and DOR of 14 mi RNAs(6up-regulated and 8 down-regulated)in the diagnosis of neonatal HIE were0.84(95% CI: 0.81-0.85),0.82(95%CI: 0.80-0.85)and 38.81(95%CI:21.50-70.05),respectively,and the AUC and Q * index were 0.9207 and0.8542,respectively.Subgroup analysis showed that these mi RNAs had better diagnostic performance for HIE among Chinese than non-Chinese;The diagnostic performance of mi RNAs in the venous blood samples of children after birth is better than that of umbilical cord blood samples,and the diagnostic ability of mi RNAs with up-regulated expression is significantly better than that of mi RNAs with down-regulated expression.In addition,four mi RNAs(mi R-210,mi R-374 a,mi R-410 and mi R-384)can distinguish neonatal HIE of different severity.In addition,no publication bias was found.2.Differential expression analysis was performed on the expression profile data of HIE samples and control samples,and 1442 differentially expressed m RNAs and 2432 differentially expressed Circ RNAs were obtained.397 differentially expressed mi RNA target genes were identified,which are mainly involved in the regulation of functions and pathways such as immunity,inflammation,circadian rhythm,cell death,metabolism,vascular and nervous system development.Fifteen key target genes(CDKN1A,CD163,CX3CL1,CXCL1,TGFBR1,DNMT1,HIF1 A,PTK2,EGR1,FN1,IL10,MYCN,CDH2,ERBB2,ITGB1)were identified based on PPI network.Finally,the ce RNA network of circ RNA-mi RNA-m RNA was constructed based on diagnostic mi RNAs.Mi RNA-regulated transcription factors(MCYN,MR2F2)were predicted based on the database.In particular,MCYN was regulated by ce RNA network bridging hsa-mi R-429 and hsa-mi R-5195-3p.Conclusions:1.This study shows that the combination of mi RNAs in blood has a high accuracy in the diagnosis of neonatal HIE,and can distinguish HIE of different severity to a certain extent.2.Diagnostic mi RNAs may participate in the occurrence and development mechanism of HIE by participating in biological mechanisms such as immunity,inflammation,circadian rhythm,cell death,metabolism,vascular and nervous system development.3.Large-scale and high-quality basic and clinical studies are needed to validate the results of this study and confirm the clinical potential of these diagnostic mi RNAs and their upstream and downstream regulatory molecules in neonatal HIE.