| Background:Sepsis is caused by the invasion of pathogenic microorganisms and the host’s loss of control of the response,which can eventually lead to life-threatening multi-organ dysfunction.The pathogenesis of sepsis is complex,and there is currently a lack of reliable diagnostic biomarkers.Our previous research identified a set of differentially expressed genes,such as BATF,C3AR1,CEACAM4,GNA15,JUNB,MTCH1,and TGFB1,with good diagnostic efficiency for sepsis in clinical sample cohort in the early stage.Objective:In this study,we aimed to validate and further screen this set of differentially expressed genes,explore the correlation between the expression levels of each gene in the gene set and sepsis prognosis,screen for differentially expressed genes that affect sepsis prognosis,and analyze their predictive value for sepsis prognosis.Method:Adopting the cecal ligation and puncture(CLP)method to construct a sepsis model.The expression levels of inflammatory factors were detected,and the reliability of the model was verified by survival curve.Differential gene expression levels were detected using digital PCR.Blood samples and relevant clinical indicators were prospectively collected from sepsis patients,and their prognosis was followed up.Using digital PCR method to detect the gene expression level of patients and analyzing the expression differences of genes between the survivors and non-survivors group.Risk factors for 90-day mortality in sepsis were analyzed using univariate analysis,and independent risk factors for 90-day mortality in sepsis were analyzed using binary logistic regression.The predictive value of differential gene expression for sepsis prognosis was evaluated using ROC curves.A lentivirus vector was used to inhibit differential gene expression in septic mice,ELISA and immunofluorescence were used to detect the inflammatory cytokines,and to evaluate the role of differential gene in the occurrence and development of sepsis.Result:In the sepsis model of this study,the expression levels of BATF,C3AR1,JUNB,and MTCH1 gene were significantly increased compared to sham group(P<0.05).A total of 53 sepsis patients were included for final analysis.Among them,the expression levels of BATF gene were significantly increased in the non-survivors group(28 days,P=0.0423;90 days,P=0.0503),while there was no statistical difference in the expression of C3AR1,JUNB,and MTCH1 genes between the two groups(P>0.05).Binary logistic regression analysis found that BATF gene was an independent risk factor for 90-day mortality in sepsis patients(OR=0.016,P<0.001).ROC curves showed that BATF expression level(AUC=0.678,P=0.05)and APACHE Ⅱ score(AUC=0.736,P=0.009)could predict 90-day mortality in sepsis patients,and the combination of BATF and APACHE II score(AUC=0.845,P<0.001)showed great diagnostic efficacy.After inhibiting the BATF gene,the levels of IL-6,IFN-γ,and TNF-α significantly decreased(P<0.05)in the sepsis model,and the survival rate of the mice increased(CLP vs BATF-shRNA+CLP,40%vs 70%).Conclusions:High expression of BATF gene is an independent risk factor for the 90-day prognosis of sepsis patients,the combination of BATF and APACHE Ⅱ score showed great diagnostic efficacy.Inhibiting BATF expression can effectively reduce sepsis mortality and may provide new ideas for sepsis prognosis prediction and treatment direction. |
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