Study on the Predictive Value of miR-200a and miR-4652-3p Levels in Cerebrospinal Fluid of Patients with Tuberculous Meningitis for Disease Severity and Prognosis
Objective To analyze the expression of microRNA(miR)-200a and miR-4652-3p in cerebrospinal fluid of patients with tuberculous meningitis(TBM)and their predictive value for disease severity and prognosis.Methods A total of 187 patients with tuberculous meningitis who visited Qingdao Chest Hospital from January 2018 to December 2022 were regarded and separated into stage Ⅰ(n=62),stage Ⅱ(n=76)and stage Ⅲ(n=49)according to the severity of the condition.There were 131 cases in the good prognosis group and 56 cases in the poor prognosis group according to the prognosis.The qRT-PCR method was applied to detect the expression levels of miR-200a and miR-4652-3p in cerebrospinal fluid.Spearman method was used to analyze correlation among miR-200a,miR-4652-3p and clinical data.ROC curve was applied to analyze the predictive value of cerebrospinal fluid miR-200a and miR-4652-3p levels in evaluating the severity and prognosis of tuberculosis meningitis patients.Multivariate logistic regression was applied to analyze the influencing factors of poor prognosis in patients.Results The expression levels of miR-200a(1.05±0.14,0.91±0.14,0.76±0.13)and miR-4652-3p(0.92±0.11,0.78±0.11,0.65±0.10)in the cerebrospinal fluid of patients with stage Ⅰ,Ⅱ,and Ⅲ tuberculous meningitis were decreased sequentially,and the differences were significant(F=61.079,87.203,all P＜0.05).The expression levels of miR-200a(0.95±0.14)and miR-4652-3p(0.82±0.11)in cerebrospinal fluid of patients with good prognosis tuberculous meningitis were higher than those of patients with poor rognosis(0.84±0.13,0.73±0.10),and the differences were statistically significant(t=5.025,5.262,all P＜0.05),while the levels of cerebrospinal fluid adenosine deaminase,TNF-α,IL-23,LTB4,CRP and mRS scores in patients with good prognosis were lower than those in patients with poor prognosis(t=5.649,7.721,11.150,9.455,11.314,14.407,all P＜0.05).There was a positive correlation between the levels of miR-200a and miR-4652-3p in cerebrospinal fluid of patients with tuberculous meningitis(r=0.405,P＜0.001).The levels of miR-200a and miR-4652-3p in cerebrospinal fluid were negatively correlated with LTB4,TNF-ot,CRP,mRS scores,IL-23 and adenosine deaminase(r=-0.472,-0.466,-0.461,-0.435,-0.422,-0.419;-0.459,-0.531,-0.471,-0.417,-0.513,-0.408,all P＜0.05).The AUC(95％CI)of miR-200a and miR-4652-3p to assess disease severity were 0.881(0.825～0.923)and 0.878(0.822～0.921),respectively.The AUC(95％CI)of both combination in assessing the severity of patients was 0.945(0.902～0.973),which was higher than the single detection,and the differences were significant(Z=3.008,2.960,all P=0.003).The AUC(95％CI)of poor prognosis patients evaluated by cerebrospinal fluid miR-200a and miR-4652-3p levels were 0.749(0.681～0.809)and 0.756(0.688～0.816),and the AUC of poor prognosis patients evaluated by both combination was 0.839(0.778～0.889),which was higher than that measured separately,and the differences were significant(Z=2.994,2.697,P=0.003,0.007).Adenosine deaminase[OR(95％CI):1.106(1.033～1.185)],miR-200a[OR(95％CI):0.529(0.369～0.744)],miR-4652-3p[OR(95％CI):0.471(0.310～0.715)],C-reactive protein[OR(95％CI):4.423(1.459～13.412)],TNF-α[OR(95％CI):1.196(1.061～1.348)],IL-23[OR(95％CI):4.809(1.086～3.013)],and LTB4[OR(95％CI):1.327(1.064～1.655)]were influencing factors for poor prognosis in patients with tuberculous meningitis(all P＜0.05).Conclusion The expressions of miR-200a and miR-4652-3p in cerebrospinal fluid of patients with tuberculous meningitis were down-regulated,and they were closely related to the severity and prognosis of the disease.The combination of the miR-200a and miR-4652-3p could better predict the severity and prognosis of tuberculous meningitis,which may have a certain clinical value.
国家科技期刊平台
NSTL
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