Correlation between exosomal miR-335-5p and severity of cirrhosis in patients with chronic hepatitis B
Objective To investigate the relationship between exosomal microRNA(miR)-335-5p and the severity of cirrhosis in patients with chronic hepatitis B(CHB),in order to provide more clinical information for early intervention and treatment.Methods From February to August 2019,6 healthy controls,8 cases of compensated cirrhosis(CLC),and 8 cases of decompensated cirrhosis(DLC)were recruited from the physical examination outpatient department and the hepatology department of Peking University Third Hospital Qinhuangdao Hospital as a discovery cohort,and serum samples were collected for exosome extraction and miRNA microarray analysis.A validation cohort of 229 CHB patients with cirrhosis,including 94 CLC and 135 DLC patients,was selected from those diagnosed and treated in the hepatology department of the hospital from December 2019 to May 2022.Exosomes were extracted and identified,and the expression level of serum exosomal miR-335-5p was detected by real-time fluorescence quantitative PCR.The model for end-stage liver disease(MELD)score and the combined formula of serum sodium with MELD(MELD-Na)score were used to evaluate the severity of cirrhosis.Results In the discovery cohort,the expression of miR-335-5p in the DLC group was significantly down-regulated compared to the control group and CLC group(P＜0.05).In the validation cohort,the level of exosomal miR-335-5p in the DLC group was significantly lower than that in the CLC group(P＜0.001).Spearman correlation analysis showed a negative correlation between the expression of exosomal miR-335-5p and both MELD and MELD-Na scores in patients with cirrhosis(P＜0.05).After adjusting for other confounding factors in the multiple linear regression model,the expression of exosomal miR-335-5p was still negatively correlated with MELD score(β=-0.103,95％CI:-3.692 to-1.149,P＜0.001)and MELD-NA score(β=-0.109,95％CI:-4.007 to-1.270,P＜0.001).ROC curve analysis indicated that serum exosomal miR-335-5p could differentiate DLC with an area under the ROC curve of 0.905(95％CI:0.867 to 0.944),corresponding to a cutoff value of 0.158,with a specificity of 87.2％,and a sensitivity of 83.7％.Conclusions The low expression of exosomal miR-335-5p is associated with the aggravation of cirrhosis in CHB patients,and may serve as a useful biomarker for the early diagnosis of DLC.
NETL
NSTL
万方数据
