Plasma-Derived Exosomal SncRNA as a Promising Diagnostic Biomarker for Early Detection of HBV-Related Acute-on-Chronic Liver Failure.
Plasma-Derived Exosomal SncRNA as a Promising Diagnostic Biomarker for Early Detection of HBV-Related Acute-on-Chronic Liver Failure.
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DOI：
10.3389/fcimb.2022.923300
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发表时间：
2022
影响因子：
5.7
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中科院分区：
文献类型：
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小非编码rna （sncRNAs）包括microRNAs和非规范sncRNAs[即trna衍生的小rna （tsRNAs）和rrna衍生的小rna (rsRNAs)]是一类重要的基因调控因子，可用于应对多种疾病。我们专注于在乙型肝炎病毒（HBV）相关的急性慢性肝衰竭（ACLF）中富集的sncRNA特征，以开发一种基于血浆外泌体的人类ACLF非侵入性生物标志物。在这项工作中，通过小RNA测序（RNA-seq）在发现队列中的3名正常受试者，4名慢性乙型肝炎（CHB）发作患者和6名HBV-ACLF患者的血浆外泌体中鉴定出与HBV-ACLF相关的sncRNAs。随后，在验证队列（n = 313）中，使用新开发的包含不同mi/ts/rsRNAs（称为mtr - rna）的分子特征，通过qRT-PCR分析进一步验证差异表达的sncRNAs。随后，利用最小绝对收缩和选择算子（LASSO）逻辑回归（LR）模型分析，我们开发了一种用于ACLF早期检测的mrr - rna分类器。鉴定出的sncrna （hsa-miR-23b-3p、hsa-miR-223-3p、hsa-miR-339-5p、tsRNA-20、tsRNA-46和rsRNA-249）在HBV-ACLF的血浆外泌体中特异性表达差异。含有上述sncRNAs的MTR-RNA特征（AUC = 0.787）在正常受试者、CHB发作患者（AUC = 0.694，敏感性85.71% /特异性59.5%）和CHB/肝硬化患者（AUC = 0.785，敏感性57.14% /特异性94.59%）中区分HBV-ACLF病例的特异性为71.67%和74.29%。值得注意的是，在检测患者或正常人时，其特异性为100% /灵敏度为94.80%。我们构建的血浆源性外泌体sncRNA特征可以作为ACLF检测的可靠生物标志物，也可以作为选择可以从辅助治疗中获益的病例的前分诊生物标志物。
The small noncoding RNAs (sncRNAs) including microRNAs and the noncanonical sncRNAs [i.e., tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs)] are a vital class of gene regulators in response to a variety of diseases. We focus on an sncRNA signature enriched in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) to develop a plasma exosome-based noninvasive biomarker for human ACLF. In this work, sncRNAs related to HBV-ACLF were identified by small RNA sequencing (RNA-seq) in plasma exosomes collected from 3 normal subjects, 4 chronic hepatitis B (CHB) patients with flare, and 6 HBV-ACLF patients in the discovery cohort. Thereafter, the differentially expressed sncRNAs were further verified in a validation cohort (n = 313) using the newly developed molecular signature incorporating different mi/ts/rsRNAs (named as MTR-RNAs) through qRT-PCR assays. Subsequently, using the least absolute shrinkage and selection operator (LASSO) logistic regression (LR) model analysis, we developed an MTR-RNA classifier for early detection of ACLF. The identified sncRNAs (hsa-miR-23b-3p, hsa-miR-223-3p, hsa-miR-339-5p, tsRNA-20, tsRNA-46, and rsRNA-249) were specifically differentially expressed in plasma exosomes of HBV-ACLF. The MTR-RNA signature (AUC = 0.787) containing the above sncRNAs distinguished HBV-ACLF cases among normal subjects with 71.67% specificity and 74.29% sensitivity, CHB patients with flare (AUC = 0.694, 85.71% sensitivity/59.5% specificity), and patients with CHB/cirrhosis (AUC = 0.785, 57.14% sensitivity/94.59% specificity). Notably, it revealed 100% specificity/94.80% sensitivity in detecting patients or normal people. Our as-constructed plasma-derived exosomal sncRNA signature can serve as a reliable biomarker for ACLF detection and also be adopted to be the pre−triage biomarker for selecting cases that can gain benefits from adjuvant treatment.
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