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Plasma-Derived Exosomal SncRNA as a Promising Diagnostic Biomarker for Early Detection of HBV-Related Acute-on-Chronic Liver Failure

OBJECTIVES: 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 hepatit...

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Autores principales: Xu, Wenli, Yu, Mingxue, Wu, Yuankai, Jie, Yusheng, Li, Xiangyong, Zeng, Xinxin, Yang, Fangji, Chong, Yutian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301338/
https://www.ncbi.nlm.nih.gov/pubmed/35873157
http://dx.doi.org/10.3389/fcimb.2022.923300
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author Xu, Wenli
Yu, Mingxue
Wu, Yuankai
Jie, Yusheng
Li, Xiangyong
Zeng, Xinxin
Yang, Fangji
Chong, Yutian
author_facet Xu, Wenli
Yu, Mingxue
Wu, Yuankai
Jie, Yusheng
Li, Xiangyong
Zeng, Xinxin
Yang, Fangji
Chong, Yutian
author_sort Xu, Wenli
collection PubMed
description OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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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spelling pubmed-93013382022-07-22 Plasma-Derived Exosomal SncRNA as a Promising Diagnostic Biomarker for Early Detection of HBV-Related Acute-on-Chronic Liver Failure Xu, Wenli Yu, Mingxue Wu, Yuankai Jie, Yusheng Li, Xiangyong Zeng, Xinxin Yang, Fangji Chong, Yutian Front Cell Infect Microbiol Cellular and Infection Microbiology OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Frontiers Media S.A. 2022-07-07 /pmc/articles/PMC9301338/ /pubmed/35873157 http://dx.doi.org/10.3389/fcimb.2022.923300 Text en Copyright © 2022 Xu, Yu, Wu, Jie, Li, Zeng, Yang and Chong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Xu, Wenli
Yu, Mingxue
Wu, Yuankai
Jie, Yusheng
Li, Xiangyong
Zeng, Xinxin
Yang, Fangji
Chong, Yutian
Plasma-Derived Exosomal SncRNA as a Promising Diagnostic Biomarker for Early Detection of HBV-Related Acute-on-Chronic Liver Failure
title Plasma-Derived Exosomal SncRNA as a Promising Diagnostic Biomarker for Early Detection of HBV-Related Acute-on-Chronic Liver Failure
title_full Plasma-Derived Exosomal SncRNA as a Promising Diagnostic Biomarker for Early Detection of HBV-Related Acute-on-Chronic Liver Failure
title_fullStr Plasma-Derived Exosomal SncRNA as a Promising Diagnostic Biomarker for Early Detection of HBV-Related Acute-on-Chronic Liver Failure
title_full_unstemmed Plasma-Derived Exosomal SncRNA as a Promising Diagnostic Biomarker for Early Detection of HBV-Related Acute-on-Chronic Liver Failure
title_short Plasma-Derived Exosomal SncRNA as a Promising Diagnostic Biomarker for Early Detection of HBV-Related Acute-on-Chronic Liver Failure
title_sort plasma-derived exosomal sncrna as a promising diagnostic biomarker for early detection of hbv-related acute-on-chronic liver failure
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301338/
https://www.ncbi.nlm.nih.gov/pubmed/35873157
http://dx.doi.org/10.3389/fcimb.2022.923300
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