HBV相关慢加急性肝衰竭患者血清miRNA表达谱及临床预测价值

MiRNA expression profiles and predictive value in patients with hepatitis B-related acute on chronic liver failure

目的分析乙型肝炎病毒(HBV)相关慢加急性肝衰竭(HBV-ACLF)与慢性乙型肝炎(CHB)患者血清中微小RNA(miRNA)差异表达谱,寻找HBV-ACLF具有预测价值的miRNA标志物。方法采用miRNA芯片技术检测10例HBV-ACLF患者和5例CHB患者血清中miRNA的差异表达,筛选出差异明显的miRNA,应用受试者工作特征曲线(ROC曲线)进一步评价其在HBV-ACLF中的预测价值。结果与CHB组相比,HBV-ACLF组中17种miRNA表达下调,两组之间差异有统计学意义(P<0.05),9种miRNA表达上调,差异有统计学意义(P<0.05)。HBV-ACLF组表达上调超过2倍的miRNA有hsa-miR-4281、hsa-miR-6126、hsa-miR-1275,表达下调超过2倍的miRNA有hsa-miR-15a-5p、hsa-miR-92b-3p、hsa-miR-25-3p、hsa-miR-92a-3p、hsa-miR-106b-5p、hsa-miR-140-3p、hsa-miR-16-5p、hsa-miR-451a、hsa-miR-486-5p。ROC曲线分析结果表明,hsa-miR-4281、hsa-miR-6126、hsa-miR-16-5p、hsa-miR-25-3p等4种miRNA在ROC曲线下面积超过0.800,其中hsa-miR-4281对HBVACLF预测的灵敏度及特异度最高。结论HBV-ACLF与CHB患者血清中miRNA谱存在表达差异,hsa-miR-4281在预测HBV-ACLF严重性方面有一定价值。

Objective To analyze the differential expression profilies of microRNA（miRNA）in serum of patients with hepatitis B virus-related acute on chronic liver failure（HBV-ACLF）and chronic hepatitis B（CHB）,and identify the miRNA markers for predictive value of HBV-ACLF.Methods Serum miRNA expression profiles of 10 patients with HBV-ACLF and 5patients with CHB were detected by using miRNA microarray and predictive value of miRNA was analyzed by receiver operating characteristic（ROC）curve.Results Compared with the CHB group,the expression of 17 kinds of miRNA in HBV-ACLF group was down regulated,the difference between the two groups was statistically significant（P〈0.05）,the 9kinds of miRNA expression were up-regulated,and the difference was statistically significant（P〈0.05）.The levels of hsa-miR-4281,hsa-miR-6126 and hsa-miR-1275 in HBV-ACLF patients were more than two times higher than in CHB patients,and the level of hsa-miR-15a-5p,hsa-miR-92b-3p,hsa-miR-25-3p,hsa-miR-92a-3p,hsa-miR-106b-5p,hsa-miR-140-3p,hsa-miR-16-5p,hsa-miR-451 aand hsa-miR-486-5p in HBV-ACLF patients were more than two times lower than in CHB patients.ROC curve analysis indicated the AUC value of hsa-miR-4281,hsa-miR-6126,hsamiR-16-5p and hsa-miR-25-3p was more than 0.800,among them,the sensitivity and specificity of hsa-miR-4281 was the highest.Conclusion The miRNA expression profil are different between HBV-ACLF and HBV patients,and hsa-miR-4281 could be a potential biomarker for HBV-ACLF patients.