乙型肝炎肝纤维化患者的外泌体、血清及肝组织中miR-92a-3p的表达及意义

摘要/Abstract

摘要： 目的探讨乙型肝炎肝纤维化患者的外泌体、血清及肝组织中miR-92a-3p的表达及意义。方法实时荧光定量PCR检测乙型肝炎患者肝纤维化不同阶段的外泌体、血清及肝组织中miR-92a-3p的表达水平。比较miR-92a-3p在肝纤维化不同时期表达水平的差异使用Mann -Whitney秩和检验或Kruskal-Wallis 检验;采用Spearman相关分析miR-92a-3p表达水平在外泌体、血清及肝组织中的相关性。应用受试者工作特征曲线下面积(AUC)评估外泌体miR-92a-3p和血清miR-92a-3p对乙型肝炎显著性肝纤维化的预测效能。结果外泌体 miR-92a-3p的表达量在肝纤维化不同分期差异显著(P<0.05),S2-4期外泌体miR-92a-3p的表达量显著高于S0-1期(P<0.0001);血清miR-92a-3p在S0-1期、S2期、S3期及S4期的相对表达量分别为0.69±0.20、1.35±1.01、0.88±0.74、0.87±1.33,差异无统计学意义(F=3.06,P=0.381);肝组织miR-92a-3p在S0-1期、S2期、S3期及S4期的相对表达量分别为1.69±1.31、1.54±1.26、1.05±0.61、0.68±0.54,差异无统计学意义(F=6.16,P=0.104)。外泌体miR-92a-3p的表达水平与血清miR-92a-3p没有显著的相关性(r=0.1787, P=0.108),外泌体miR-92a-3p的表达水平与肝组织miR-92a-3p也没有显著的相关性(r=0.051, P=0.731)。当cut-off 值为0.245时,血清miR-92a-3p的AUC为0.61(95% CI: 0.48~0.75),对显著性肝纤维化诊断的敏感度和特异度分别为63.46%和 60%;外泌体miR-92a-3p在cut-off 值为0.7459时,AUC为0.87(95% CI: 0.80~0.94),诊断显著性肝纤维化的敏感度和特异度分别为84.13%和72.09%。结论 miR-92a-3p的表达水平在外泌体、血清及肝组织没有显著相关性。miR-92a-3p 在外泌体的浓度显著高于血清和肝组织,与血清miR-92a-3p相比,外泌体miR-92a-3p对乙型肝炎患者显著性肝纤维化的诊断效能更高。

关键词: miR-92a-3p, 外泌体, 血清, 肝组织, 肝纤维化

Abstract: Objective To investigate the expression levels of microRNA miR-92a-3p in exosomes, serum and liver tissue samples of patients with HBV-related hepatic fibrosis and to analyze the difference and significance. Methods Real-time fluorescent quantitative PCR technology was used to detect the expression levels of miR-92a-3p in exosomes, serum, and liver tissue of patients with hepatitis B-related liver fibrosis at different stages. The Mann-Whitney U test or Kruskal-Wallis test was used to compare the differences in miR-92a-3p expression levels during different stages of liver fibrosis. Spearman’s correlation coefficient method was employed to analyze the correlation between the level of miR-92a-3p in exosomes and that in serum and liver tissue. The receiver operating characteristic curve (ROC) was applied to evaluate the predictive efficacy of exosomal and serum miR-92a-3p levels for significant liver fibrosis in hepatitis B. Results The expression level of miR-92a-3p in exosomes showed significant differences among different stages of liver fibrosis (P<0.05). The expression level of miR-92a-3p in exosomes from patients in S2-4 stages was significantly higher than that in S0-1 stages (P<0.0001). The relative expression levels of serum miR-92a-3p in S0-1, S2, S3 and S4 stages were 0.69±0.20, 1.01±1.35, 0.74±0.88 and 0.87±1.33, respectively. There was no statistically significant difference in the expression level of miR-92a-3p in serum among different stages of liver fibrosis (P=0.3817). The relative expression levels of liver tissue miR-92a-3p in S0-1, S2, S3 and S4 stages were 1.69±1.31, 1.54±1.26, 1.05±0.61 and 0.68±0.54, respectively. Similarly, no statistically significant difference was observed in the expression level of miR-92a-3p in liver tissue among different stages of liver fibrosis (P=0.1040). The expression level of miR-92a-3p in exosomes did not show a significant correlation with its expression level in serum (r=0.1787, P=0.1083). Similarly, there was no significant correlation between the expression levels of miR-92a-3p in exosomes and liver tissue (r=0.051, P=0.7311). When the cut-off value was 0.245, the AUROC for serum miR-92a-3p was 0.61 (95%CI: 0.48~0.75), with a sensitivity and specificity for diagnosing significant liver fibrosis of 63.46% and 60%, respectively. For exosomal miR-92a-3p, at a cut-off value of 0.7459, the AUROC was highest at 0.87 (95%CI: 0.80~0.94), with a sensitivity and specificity for diagnosing significant liver fibrosis of 84.13% and 72.09%, respectively. Conclusion The expression levels of miR-92a-3p in exosomes, serum, and liver tissue showed no significant correlation. The concentration of miR-92a-3p in exosomes is significantly higher than in serum and liver tissue, indicating that circulating miR-92a-3p is enriched in exosomes. Compared to serum miR-92a-3p, exosomal miR-92a-3p demonstrated higher diagnostic efficacy for significant liver fibrosis in hepatitis B patients.

Key words: miR-92a-3p, Exosomes, Serum, Liver tissue, Liver fibrosis

王倩倩, 蒋旭华, 李新艳, 宋杰, 张毅, 季媛媛, 任晓静, 戚勋, 陈良, 张键, 黄玉仙. 乙型肝炎肝纤维化患者的外泌体、血清及肝组织中miR-92a-3p的表达及意义[J]. 肝脏, 2024, 29(11): 1325-1329.

WANG Qian-qian, JIANG Xu-hua, LI Xin-yan, SONG Jie, ZHANG Yi, JI Yuan-yuan, REN Xiao-jing, QI Xun, CHEN Liang, ZHANG Jian, HUANG Yu-xian. The expression levels and significance of miR-92a-3p in exosomes, serum and liver tissue of patients with hepatitis B-related liver fibrosis[J]. Chinese Hepatolgy, 2024, 29(11): 1325-1329.

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