Background Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children.It is associated with high rates of morbidity...Background Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children.It is associated with high rates of morbidity and mortality,and rapid detection and administration of antimicrobials have been emphasized.The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness.Methods Three gene expression datasets were available from the Gene Expression Omnibus collection.First,the differentially expressed genes(DEGs)were found with the use of the R program,and then gene set enrichment analysis was carried out.Subsequently,the DEGs were combined with the major module genes chosen using the weighted gene co-expression network.The hub genes were identified by the use of three machine-learning algorithms:random forest,support vector machine-recursive feature elimination,and least absolute shrinkage and selection operator.The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes.In addition,the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts(CIBERSORT).The relationship between the diagnostic markers and infiltrating immune cells was further studied.Results Overall,after overlapping key module genes and DEGs,we detected 402 overlapping genes.As pediatric sepsis diagnostic indicators,CYSTM1(AUC=0.988),MMP8(AUC=0.973),and CD177(AUC=0.986)were investigated and demonstrated statistically significant differences(P<0.05)and diagnostic efficacy in the validation set.As indicated by the immune cell infiltration analysis,multiple immune cells may be involved in the development of pediatric sepsis.Additionally,all diagnostic characteristics may correlate with immune cells to varying degrees.Conclusions The candidate hub genes(CD177,CYSTM1,and MMP8)were identified,and the nomogram was constructed for pediatric sepsis diagnosis.Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.展开更多
基金supported by the Key R&D Program of Zhejiang(2022C03163 to X.F.).National Key Research and Development Program of China(2018YFC2001905 to X.A.)+1 种基金the National Natural Science Foundation of China(NSFC)(82230074 to X.F.,82072221 to K.Z.)the Natural Science Foundation of Zhejiang Province(LZ22H150002 to K.Z.).
文摘Background Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children.It is associated with high rates of morbidity and mortality,and rapid detection and administration of antimicrobials have been emphasized.The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness.Methods Three gene expression datasets were available from the Gene Expression Omnibus collection.First,the differentially expressed genes(DEGs)were found with the use of the R program,and then gene set enrichment analysis was carried out.Subsequently,the DEGs were combined with the major module genes chosen using the weighted gene co-expression network.The hub genes were identified by the use of three machine-learning algorithms:random forest,support vector machine-recursive feature elimination,and least absolute shrinkage and selection operator.The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes.In addition,the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts(CIBERSORT).The relationship between the diagnostic markers and infiltrating immune cells was further studied.Results Overall,after overlapping key module genes and DEGs,we detected 402 overlapping genes.As pediatric sepsis diagnostic indicators,CYSTM1(AUC=0.988),MMP8(AUC=0.973),and CD177(AUC=0.986)were investigated and demonstrated statistically significant differences(P<0.05)and diagnostic efficacy in the validation set.As indicated by the immune cell infiltration analysis,multiple immune cells may be involved in the development of pediatric sepsis.Additionally,all diagnostic characteristics may correlate with immune cells to varying degrees.Conclusions The candidate hub genes(CD177,CYSTM1,and MMP8)were identified,and the nomogram was constructed for pediatric sepsis diagnosis.Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.