Identification of prognostic long non-coding RNA and construction of competing endogenous RNA networks in pediatric sepsis

doi:10.3969/j.issn.1674-8115.2025.03.004

Abstract

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.

Key words: pediatric sepsis, long non-coding RNA, competing endogenous RNA, prognostic biomarker

CLC Number:

R737.9

LIU Tiantian, ZHAO Yilin, NING Jingjing, ZHANG Yucai, WANG Chunxia. Identification of prognostic long non-coding RNA and construction of competing endogenous RNA networks in pediatric sepsis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(3): 282-291.

Figures/Tables 8

Tab 1 Detailed information of the four microarray datasets used in the work

Item	GSE4607	GSE26440	GSE26378	GSE9692
Tissue	Whole blood	Whole blood	Whole blood	Whole blood
Platform	GPL570	GPL570	GPL570	GPL570
Sepsis shock/n
Survivor	33	81	70	24
Non-survivor	9	17	12	6
Age/year
Survivor	3.8±3.3	3.4±3.0	3.9±3.2	‒
Non-survivor	3.9±4.1	3.2±3.4	2.6±3.6	‒
Gender (male/female)/n
Survivor	19/14	‒	‒	12/12
Non-survivor	7/2	‒	‒	4/2
Timing of mortality/d	28	28	28	28

Fig 1 Flowchart for bioinformatics analysis in this work

Fig 2 The differentially expressed lncRNAs between survivors andnon-survivors of patients with sepsis

Fig 3 Construction and validation of the 6-lncRNA signature (lncSig6)

Fig 4 Subcellular localization analysis of the differentially expressed lncRNAs in the lncSig6 signature

Fig 5 The triple ceRNA regulatory network (lncRNAmiRNAmRNA) associated with the prognosis of pediatric septic shock

Fig 6 Protein interaction analysis of ceRNA network

Fig 7 Functional enrichment analysis of mRNAs in the ceRNA network

TrendMD

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