Screening of core genes prognostic for sepsis and construction of a ceRNA regulatory network

Abstract

Abstract Objective To screen out core genes potentially prognostic for sepsis and construct a competing endogenous RNA (ceRNA) regulatory network. Methods Subjects included in this project were 23 sepsis patients and 10 healthy people. RNA-seq for lncRNA, miRNA and mRNA was performed in the peripheral blood samples. Differentially expressed RNAs (DER) were screened out for further analysis. GO annotation and GSEA functional clustering were performed to view the functional enrichment of DEmRNAs. Core genes of prognostic significance were screened out with the weighted correlation network analysis (WGCNA). Meta-analysis and Survival analysis was devised in different microarray datasets. RT-qPCR was conducted to validate these core genes. A ceRNA network was accordingly constructed according to the correlation analysis and molecular interaction prediction. Results RNA-seq and differential analysis screened out 1,044 DEmRNAs, 66 DEmiRNAs and 155 DElncRNAs. The GO and GSEA analysis revealed that DEmRNAs are mainly involved in inflammatory response, immune regulation, neutrophil activation. WGCNA revealed 4 potential core genes, including CD247, IL-2Rβ, TGF-βR3 and IL-1R2. In vitro cellular experiment showed up-regulated expression of IL-1R2 while down-regulated of CD247, IL-2Rβ, TGF-βR3 in sepsis patients. Correspondingly, a ceRNA regulatory network was build based on the core genes, and multiple lncRNAs and miRNAs were identified to have a potential regulatory role in sepsis. Conclusion This study identified four core genes, including CD247, IL-1R2, IL-2Rβ and TGF-βR3, with potential to be novel biomarkers for the prognosis of sepsis. In the meantime, a ceRNA network was constructed aiming to guide further study on prognostic mechanism in sepsis.

Keywords

• Sepsis
• Prognosis
• RNA-seq
• Messenger RNA (mRNA)
• MicroRNA (miRNA)
• Long non-coding RNA (lncRNA)