Screening of potential core genes in the peripheral blood of adult patients with sepsis based on immunoregulation and signal transduction functions.

OBJECTIVE: Based on the functions of immunoregulation and signal transduction, septic peripheral blood sequencing and bioinformatics technology were used to screen potential core targets.

METHODS: Peripheral blood of twenty-three patients with sepsis and ten normal volunteers underwent RNA-seq processing within 24 hours after admission to the hospital. Data quality control and differential gene screening were performed based on R language (P < 0.01; log2FC ≥ 2). Gene function enrichment analysis was conducted on differentially expressed genes. Then, target genes were submitted to STRING to constitute the PPI network, and GSE65682 were used to explore the prognostic relevance of potential core genes. Meta-analysis was used to verify the expression trends of core genes in the sepsis group. Then, cell line localization analysis of core genes in the 5 PBMC samples (NC = 2; SIRS = 1; SEPSIS = 2) was performed.

RESULTS: A total of 1128 DEGs were obtained between sepsis and normal group, of which 721 were upregulated and 407 downregulated. These DEGs were mainly enriched in leukocyte-mediated cytotoxicity, cell killing regulation, adaptive immune response regulation, lymphocyte-mediated immune regulation, and negative regulation of adaptive immune response. PPI network analysis results showed that CD160, KLRG1, S1PR5, and RGS16 were located in the core area, which are related to adaptive immune regulation, signal transduction, and intracellular components. The above four genes in the core area were found to be related to the prognosis of patients with sepsis, of which RGS16 was negatively correlated with the survival rate, and CD160, KLRG1, and S1PR5 were positively correlated. However, several public datasets showed that CD160, KLRG1, and S1PR5 were all downregulated in the peripheral blood of patients with sepsis, while RGS16 was upregulated in the sepsis group. Single-cell sequencing analysis showed that they were mainly expressed in NK-T cells.

CONCLUSION: CD160, KLRG1, S1PR5 and RGS16 were mainly located in human peripheral blood NK-T-cells. Sepsis participants expressed lower levels of S1PR5, CD160 and KLRG1, while Sepsis participants expressed higher levels of RGS16. This suggests that they may be potential research targets for sepsis.