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基线血清外来体来源的miRNA预测接受聚乙二醇干扰素治疗的慢 [复制链接]

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发表于 2021-3-6 19:59 |只看该作者 |倒序浏览 |打印
Baseline serum exosome-derived miRNAs predict HBeAg seroconversion in chronic hepatitis B patients treated with peginterferon
Qiankun Hu  1 , Qianqian Wang  1 , Yi Zhang  1 , Shuai Tao  1 , Xueyun Zhang  2 , Xiaoqin Liu  2 , Xinyan Li  1 , Xuhua Jiang  1 , Chenlu Huang  1 , Wei Xu  1 , Xun Qi  1 , Liang Chen  1 , Qiang Li  1 , Yuxian Huang  1   2
Affiliations
Affiliations

    1
    Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
    2
    Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.

    PMID: 33666247 DOI: 10.1002/jmv.26916

Abstract

Objective: This study aimed to explore the value of baseline serum exosome-derived miRNAs for predicting HBeAg seroconversion in chronic hepatitis B (CHB) patients treated with peginterferon (Peg-IFN).

Methods: A total of 120 treatment-naïve HBeAg-positive CHB patients who received Peg-IFN therapy (48 weeks) were enrolled. Next-generation sequencing was performed to screen the serum exosomal miRNAs that were associated with Peg-IFN treatment outcome, and qRT-PCR was used to validate them. The area under receiver operating characteristic curve (AUROC) was used to evaluate the predictive efficacy of biomarkers.

Results: Thirty-three patients (27.5%) achieved HBeAg seroconversion (response group), and 87 patients (72.5%) did not achieve HBeAg seroconversion (non-response group). In the identification cohort, forty serum exosome-derived miRNAs were differentially expressed between the response group (4 patients) and the non-response group (4 patients). In the confirmation cohort, the expression levels of serum exosomal miR-194-5p (p < 0.001) and miR-22-3p (p < 0.001) were significantly downregulated in the response group (29 patients) compared to the non-response group (83 patients). Multivariate analysis identified baseline serum exosomal miR-194-5p, miR-22-3p, alanine aminotransferase (ALT) and HBV DNA as independent predictors of HBeAg seroconversion (all p < 0.05). The AUROCs of serum exosomal miRNAs (0.77 and 0.75 for miR-194-5p and miR-22-3p, respectively) were higher than that of ALT (0.70) and HBV DNA (0.69). The combination of exosomal miR-194-5p and miR-22-3p further improved the predictive performance with an AUROC of 0.82.

Conclusion: Baseline serum exosomal miR-194-5p and miR-22-3p may serve as novel biomarkers to predict HBeAg seroconversion in CHB patients treated with Peg-IFN. This article is protected by copyright. All rights reserved.

Keywords: chronic; exosome; hepatitis B; miR-194-5p; miR-22-3p; peginterferon.

This article is protected by copyright. All rights reserved.

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发表于 2021-3-6 19:59 |只看该作者
基线血清外来体来源的miRNA预测接受聚乙二醇干扰素治疗的慢性乙型肝炎患者的HBeAg血清转化
胡前坤1,王谦谦1,张艺1,陶涛1,张学云2,刘小琴2,李新彦1,江旭华1,黄晨璐1,徐伟1,un奇1,陈亮1,李强1黄玉贤1 2
隶属关系
隶属关系

    1个
    复旦大学上海公共卫生临床中心肝病科,上海
    2个
    复旦大学附属华山医院传染病科,上海。

    PMID:33666247 DOI:10.1002 / jmv.26916

抽象的

目的:本研究旨在探讨基线血清外来体来源的miRNA在预测接受聚乙二醇干扰素(Peg-IFN)治疗的慢性乙型肝炎(CHB)患者中HBeAg血清转化的价值。

方法:共纳入120名接受Peg-IFN治疗(48周)的未接受过治疗的HBeAg阳性CHB患者。进行了下一代测序以筛选与Peg-IFN治疗结果相关的血清外泌体miRNA,并使用qRT-PCR对其进行验证。接收器工作特征曲线(AUROC)下的面积用于评估生物标志物的预测功效。

结果:33例患者(27.5%)实现了HBeAg血清转化(应答组),87例患者(72.5%)未实现HBeAg血清转化(无应答组)。在鉴定队列中,应答组(4名患者)和无应答组(4名患者)之间有40种血清外泌体来源的miRNA差异表达。在确认队列中,与无反应组相比,反应组(29例患者)的血清外体miR-194-5p(p <0.001)和miR-22-3p(p <0.001)的表达水平显着下调。 (83例)。多变量分析确定基线血清外泌体miR-194-5p,miR-22-3p,丙氨酸氨基转移酶(ALT)和HBV DNA是HBeAg血清转化的独立预测因子(所有p <0.05)。血清外泌体miRNA的AUROC(miR-194-5p和miR-22-3p分别为0.77和0.75)高于ALT(0.70)和HBV DNA(0.69)。 miR-194-5p和miR-22-3p的外体组合进一步改善了预测性能,AUROC为0.82。

结论:基线血清外泌体miR-194-5p和miR-22-3p可能是预测接受Peg-IFN治疗的CHB患者HBeAg血清转化的新型生物标志物。本文受版权保护。版权所有。

关键词:慢性外泌体乙型肝炎; miR-194-5p; miR-22-3p;聚乙二醇干扰素。

本文受版权保护。版权所有。
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