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Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients

INTRODUCTION: Acute rejection (AR) continues to be a significant obstacle for short- and long-term graft survival in kidney transplant recipients. Herein, we aimed to examine urinary exosomal microRNAs with the objective of identifying novel biomarkers of AR. MATERIALS AND METHODS: Candidate microRN...

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Autores principales: Seo, Jung-Woo, Lee, Yu Ho, Tae, Dong Hyun, Kim, Yang Gyun, Moon, Ju-Young, Jung, Su Woong, Kim, Jin Sug, Hwang, Hyeon Seok, Jeong, Kyung-Hwan, Jeong, Hye Yun, Lee, So-Young, Chung, Byung Ha, Kim, Chan-Duck, Park, Jae Berm, Seok, Junhee, Kim, Yeong Hoon, Lee, Sang-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203902/
https://www.ncbi.nlm.nih.gov/pubmed/37228607
http://dx.doi.org/10.3389/fimmu.2023.1190576
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author Seo, Jung-Woo
Lee, Yu Ho
Tae, Dong Hyun
Kim, Yang Gyun
Moon, Ju-Young
Jung, Su Woong
Kim, Jin Sug
Hwang, Hyeon Seok
Jeong, Kyung-Hwan
Jeong, Hye Yun
Lee, So-Young
Chung, Byung Ha
Kim, Chan-Duck
Park, Jae Berm
Seok, Junhee
Kim, Yeong Hoon
Lee, Sang-Ho
author_facet Seo, Jung-Woo
Lee, Yu Ho
Tae, Dong Hyun
Kim, Yang Gyun
Moon, Ju-Young
Jung, Su Woong
Kim, Jin Sug
Hwang, Hyeon Seok
Jeong, Kyung-Hwan
Jeong, Hye Yun
Lee, So-Young
Chung, Byung Ha
Kim, Chan-Duck
Park, Jae Berm
Seok, Junhee
Kim, Yeong Hoon
Lee, Sang-Ho
author_sort Seo, Jung-Woo
collection PubMed
description INTRODUCTION: Acute rejection (AR) continues to be a significant obstacle for short- and long-term graft survival in kidney transplant recipients. Herein, we aimed to examine urinary exosomal microRNAs with the objective of identifying novel biomarkers of AR. MATERIALS AND METHODS: Candidate microRNAs were selected using NanoString-based urinary exosomal microRNA profiling, meta-analysis of web-based, public microRNA database, and literature review. The expression levels of these selected microRNAs were measured in the urinary exosomes of 108 recipients of the discovery cohort using quantitative real-time polymerase chain reaction (qPCR). Based on the differential microRNA expressions, AR signatures were generated, and their diagnostic powers were determined by assessing the urinary exosomes of 260 recipients in an independent validation cohort. RESULTS: We identified 29 urinary exosomal microRNAs as candidate biomarkers of AR, of which 7 microRNAs were differentially expressed in recipients with AR, as confirmed by qPCR analysis. A three-microRNA AR signature, composed of hsa-miR-21-5p, hsa-miR-31-5p, and hsa-miR-4532, could discriminate recipients with AR from those maintaining stable graft function (area under the curve [AUC] = 0.85). This signature exhibited a fair discriminative power in the identification of AR in the validation cohort (AUC = 0.77). CONCLUSION: We have successfully demonstrated that urinary exosomal microRNA signatures may form potential biomarkers for the diagnosis of AR in kidney transplantation recipients.
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spelling pubmed-102039022023-05-24 Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients Seo, Jung-Woo Lee, Yu Ho Tae, Dong Hyun Kim, Yang Gyun Moon, Ju-Young Jung, Su Woong Kim, Jin Sug Hwang, Hyeon Seok Jeong, Kyung-Hwan Jeong, Hye Yun Lee, So-Young Chung, Byung Ha Kim, Chan-Duck Park, Jae Berm Seok, Junhee Kim, Yeong Hoon Lee, Sang-Ho Front Immunol Immunology INTRODUCTION: Acute rejection (AR) continues to be a significant obstacle for short- and long-term graft survival in kidney transplant recipients. Herein, we aimed to examine urinary exosomal microRNAs with the objective of identifying novel biomarkers of AR. MATERIALS AND METHODS: Candidate microRNAs were selected using NanoString-based urinary exosomal microRNA profiling, meta-analysis of web-based, public microRNA database, and literature review. The expression levels of these selected microRNAs were measured in the urinary exosomes of 108 recipients of the discovery cohort using quantitative real-time polymerase chain reaction (qPCR). Based on the differential microRNA expressions, AR signatures were generated, and their diagnostic powers were determined by assessing the urinary exosomes of 260 recipients in an independent validation cohort. RESULTS: We identified 29 urinary exosomal microRNAs as candidate biomarkers of AR, of which 7 microRNAs were differentially expressed in recipients with AR, as confirmed by qPCR analysis. A three-microRNA AR signature, composed of hsa-miR-21-5p, hsa-miR-31-5p, and hsa-miR-4532, could discriminate recipients with AR from those maintaining stable graft function (area under the curve [AUC] = 0.85). This signature exhibited a fair discriminative power in the identification of AR in the validation cohort (AUC = 0.77). CONCLUSION: We have successfully demonstrated that urinary exosomal microRNA signatures may form potential biomarkers for the diagnosis of AR in kidney transplantation recipients. Frontiers Media S.A. 2023-05-09 /pmc/articles/PMC10203902/ /pubmed/37228607 http://dx.doi.org/10.3389/fimmu.2023.1190576 Text en Copyright © 2023 Seo, Lee, Tae, Kim, Moon, Jung, Kim, Hwang, Jeong, Jeong, Lee, Chung, Kim, Park, Seok, Kim and Lee 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 Immunology
Seo, Jung-Woo
Lee, Yu Ho
Tae, Dong Hyun
Kim, Yang Gyun
Moon, Ju-Young
Jung, Su Woong
Kim, Jin Sug
Hwang, Hyeon Seok
Jeong, Kyung-Hwan
Jeong, Hye Yun
Lee, So-Young
Chung, Byung Ha
Kim, Chan-Duck
Park, Jae Berm
Seok, Junhee
Kim, Yeong Hoon
Lee, Sang-Ho
Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients
title Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients
title_full Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients
title_fullStr Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients
title_full_unstemmed Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients
title_short Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients
title_sort development and validation of urinary exosomal microrna biomarkers for the diagnosis of acute rejection in kidney transplant recipients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203902/
https://www.ncbi.nlm.nih.gov/pubmed/37228607
http://dx.doi.org/10.3389/fimmu.2023.1190576
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