Identification of prognostic biomarkers of sepsis and construction of ceRNA regulatory networks

Abstract

Abstract Sepsis is a life-threatening severe organ dysfunction, and the pathogenesis remains uncertain. Increasing evidence suggests that circRNAs, mRNAs, and microRNAs can interact to jointly regulate the development of sepsis. Identifying the interaction between ceRNA regulatory networks and sepsis may contribute to our deeper understanding of the pathogenesis of sepsis, bring new insights into early recognition and treatment of sepsis. Blood samples from sepsis patients in the Affiliated Hospital of Southwest Medical University were collected. RNA sequencing (mRNA/circRNA) was performed on Survivor group (n = 26) and Non-survivor group (n = 6), then quality control and differential expression analysis were performed. Subsequently, GO analysis was performed on the differential expression genes; Meta-analysis was used to screen for prognostic related genes; 10 × Single-cell RNA sequencing was used to annotate the cell distribution of core genes. Finally, combined with base complementary pairing and intergroup correlation analysis, a sepsis-associated circRNA-miRNA-mRNA regulatory network was constructed. Differential expression analysis screened 28 mRNAs and 16 circRNAs. GO results showed that differential expression genes were mainly involved in membrane raft, actin cytoskeleton, regulation of immune response, negative regulation of cAMP-dependent protein kinase activity, etc. Meta-analysis screened 2 core genes, GSPT1 and NPRL3, which are associated with sepsis prognosis. 10 × Single-cell RNA sequencing showed that GSPT1 and NPRL3 were widely localized in immune cells, mainly macrophages and T cells. A ceRNA network consisting of 4 circRNA, 26 miRNA, and 2 mRNA was constructed. GSPT1 and NPRL3 were lowly expressed in the sepsis Survivor group, compared with Non-survivor group, which may become novel prognostic biomarkers for sepsis. A sepsis-related ceRNA networks, which consists of 4 circRNA, 26 miRNA, and 2 core gene, may guide mechanistic studies.