上海交通大学学报（医学版）2025，Vol.45Issue(3)：282-291,10.DOI:10.3969/j.issn.1674-8115.2025.03.004
儿童脓毒症预后相关长链非编码RNA筛选及竞争性内源RNA网络的构建
Identification of prognostic long non-coding RNA and construction of competing endogenous RNA networks in pediatric sepsis
摘要
Abstract
Objective·To screen a long non-coding RNA(lncRNA)signature and construct a competing endogenous RNA(ceRNA)network associated with the prognosis of pediatric sepsis based on the Gene Expression Omnibus(GEO)database,and explore their potential application value in the prognosis assessment of children with sepsis.Methods·Microarray data in GSE4607,GSE26440,GSE26378,and GSE9692 in the GEO database were used to compare the differences in lncRNA profiles between the survival and non-survival groups of children with septic shock.Then,multivariate linear regression,LASSO analysis,and receiver operating characteristic(ROC)curves were used to evaluate the capacity of the lncRNA signature for predicting the outcome of pediatric sepsis.The potential targeted microRNAs(miRNAs)and their downstream mRNAs,targeted by the screened lncRNAs,were used to construct a protein-protein interaction(PPI)network and perform pathway enrichment analysis.Results·Transcriptomic data from GSE4607,GSE26440,GSE26378 and GSE9692 revealed 55 differentially expressed lncRNAs associated with prognosis,and miR503 host gene(MIR503HG),TAPT1 antisense RNA 1(TAPT1-AS1),apoptosis-associated transcript in bladder cancer(AATBC),SBF2 antisense RNA 1(SBF2-AS1),MGC16275,and small nucleolar RNA host gene 15(SNHG15)were identified as a 6-lncRNA signature(lncSig6)associated with the prognosis of pediatric septic shock by LASSO regression analysis.The area under the ROC curve(AUC)of lncSig6 was 0.859(95％CI 0.722-0.996)and 0.854(95％CI 0.687-1.000)in internal and external validation,respectively.As lncRNA act as miRNA sponge,a lncRNA-miRNA-mRNA network based on 3 lncRNAs(MIR503HG,SNHG15,and SBF2-AS1)was constructed and involved in the regulation of signaling pathways,including forkhead box O(FoxO)signaling pathway,phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT)signaling pathway,cell senescence,insulin signaling pathway,hypoxia-inducible protein-1(HIF-1)signaling pathway and advanced glycation end products(AGEs)and receptor of AGEs(RAGE)signaling pathway.Conclusion·The lncSig6 can be used as an evaluation method to predict the prognosis of septic shock in children,and the constructed ceRNA molecular networks can provide an experimental basis for the study of signaling pathways.关键词
儿童脓毒症/长链非编码RNA/竞争性内源RNA/预后标志物Key words
pediatric sepsis/long non-coding RNA/competing endogenous RNA/prognostic biomarker分类
医药卫生引用本文复制引用
刘田恬,赵奕琳,宁菁菁,张育才,王春霞..儿童脓毒症预后相关长链非编码RNA筛选及竞争性内源RNA网络的构建[J].上海交通大学学报（医学版）,2025,45(3):282-291,10.基金项目
国家自然科学基金(82171729) （82171729）
上海市自然科学基金(23ZR1453000) （23ZR1453000）
上海交通大学医学院"双百人"项目(20171928). National Natural Science Foundation of China(82171729) （20171928）
Shanghai Natural Science Foundation(23ZR1453000) （23ZR1453000）
"Two-hundred Talents"Program of Shanghai Jiao Tong University School of Medicine(20171928). （20171928）
