Diagnostic Value Of MiRNA In Gram-negative Bacteria-associated Sepsis

Objectives:To explore the diagnostic value of miRNA in Gram-negative(G~-)bacteria-related sepsis and to provide new ideas for clinical prevention and treatment of sepsis.Methods:(1)Seven patients with G~-sepsis and seven healthy subjects in the first affiliated Hospital of Dali University from September 2018 to September 2020 were selected as the screening cohort.The miRNA in serum was extracted and sequenced to screen the differentially expressed miRNA,and analyzed by bioinformatics.(2)34 patients with G~-sepsis and 16 healthy controls in the first affiliated Hospital of Dali University from September 2018 to September 2020 were selected as the validation cohort to verify the up-regulated miRNA by q RT-PCR,and to explore the diagnostic value of differentially expressed miRNA in G~-sepsis preliminarily.(3)According to the prognosis,patients with G~-sepsis were divided into survival group(n=18)and death group(n=16).The receiver operating characteristic(ROC)curve was drawn and the diagnostic value of differential miRNA and related laboratory indexes in patients with G~-sepsis was discussed.At the same time,the correlation with classical infection indexes such as PCT,CRP and SOFA score was analyzed.Results:(1)In the screening cohort,the expression levels of laboratory indexes(WBC,N,TBI,Crea),hsa-miR-1202,hsa-miR-16-5p,hsa-miR-1299,hsa-miR-486-5p and hsa-miR-451a in the G~-sepsis group were significantly higher than those in the control group(P<0.05),while the expression level of lymphocytes in the G~-sepsis group were significantly lower than those in the control group(P<0.05).In terms of diagnostic efficacy of G~-sepsis analyzed with ROC curve,the area under curve(AUC)of hsa-miR-16-5p and hsa-miR-451a was the largest(0.9796),followed by hsa-miR-1202(0.9388).(2)In the validation set,the expression levels of laboratory indexes(WBC,N,TBI,Crea,BUN),hsa-miR-16-5p,hsa-miR-1202,hsa-miR-486-5p and hsa-miR-451a in the G~-sepsis group were significantly higher than those in the healthy control group(P<0.05),while the expression level of lymphocytes in the sepsis group was significantly lower than that in the healthy control group(P<0.05).For the diagnostic value of G~-sepsis,the area under the ROC curve showed that the AUC area of hsa-miR-16-5p was the largest with an area under the curve and a 95%confidence interval of 0.74(0.59-0.85),the sensitivity and specificity for the diagnosis of G~-sepsis were 70.6%and 100.0%respectively.Followed by miR-1202,AUC area and 95%confidence interval were 0.70(0.56-0.83)and the sensitivity and specificity for the diagnosis of sepsis were 50.0%and 87.5%respectively.(3)In judging the prognosis of patients with G~-sepsis,the levels of laboratory indexes(PCT,CRP),SOFA score,hsa-miR-16-5p,hsa-miR-486-5p and hsa-miR-451a in the death group were significantly higher than those in the survival group(P<0.05).ROC curve showed that the area under the curve of hsa-miR-16-5p was the largest among the different indexes between the two groups.The area under the curve and 95%confidence interval of miR-16-5p as a prognostic marker of G~-sepsis were 0.89(0.73-0.97).The sensitivity and specificity for judging the prognosis of G~-sepsis were 68.7%and 94.4%respectively.(4)Correlation analysis showed that there was a positive correlation between miR-451a and SOFA scores,but there was no significant correlation between miR-16-5p,miR-486-5p and CRP,PCT,SOFA scores.Conclusions:Serum hsa-miR-16-5p,hsa-miR-1202,hsa-miR-486-5p and hsa-miR-451a may be biomarkers for early diagnosis of G~-sepsis.Among them,miR-16-5p has higher sensitivity and specificity,which is more helpful for the diagnosis of sepsis.Hsa-miR-16-5p,hsa-miR-486-5p and hsa-miR-451a are related to the prognosis of patients with G~-sepsis and may be potential targets for the treatment of G~-sepsis.