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Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing

Introduction: Acute cellular rejection (ACR) of heart allografts represents the most common reason for graft failure. Endomyocardial biopsies (EMB) are still subject to substantial interobserver variability. Novel biomarkers enabling precise ACR diagnostics may decrease interobserver variability. We...

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Autores principales: Nováková, Tereza, Macháčková, Táňa, Novák, Jan, Hude, Petr, Godava, Július, Žampachová, Víta, Oppelt, Jan, Zlámal, Filip, Němec, Petr, Bedáňová, Helena, Slabý, Ondřej, Bienertová-Vašků, Julie, Špinarová, Lenka, Krejčí, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912472/
https://www.ncbi.nlm.nih.gov/pubmed/31698874
http://dx.doi.org/10.3390/cells8111400
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author Nováková, Tereza
Macháčková, Táňa
Novák, Jan
Hude, Petr
Godava, Július
Žampachová, Víta
Oppelt, Jan
Zlámal, Filip
Němec, Petr
Bedáňová, Helena
Slabý, Ondřej
Bienertová-Vašků, Julie
Špinarová, Lenka
Krejčí, Jan
author_facet Nováková, Tereza
Macháčková, Táňa
Novák, Jan
Hude, Petr
Godava, Július
Žampachová, Víta
Oppelt, Jan
Zlámal, Filip
Němec, Petr
Bedáňová, Helena
Slabý, Ondřej
Bienertová-Vašků, Julie
Špinarová, Lenka
Krejčí, Jan
author_sort Nováková, Tereza
collection PubMed
description Introduction: Acute cellular rejection (ACR) of heart allografts represents the most common reason for graft failure. Endomyocardial biopsies (EMB) are still subject to substantial interobserver variability. Novel biomarkers enabling precise ACR diagnostics may decrease interobserver variability. We aimed to identify a specific subset of microRNAs reflecting the presence of ACR. Patients and Methods: Monocentric retrospective study. A total of 38 patients with the anamnesis of ACR were identified and for each patient three consecutive samples of EMB (with, prior and after ACR) were collected. Sixteen trios were used for next-generation sequencing (exploratory cohort); the resting 22 trios were used for validation with qRT-PCR (validation cohort). Statistical analysis was performed using R software. Results: The analysis of the exploration cohort provided the total of 11 miRNAs that were altered during ACR, the three of which (miR-144, miR-589 and miR-182) were further validated in the validation cohort. Using the levels of all 11 miRNAs and principal component analysis, an ACR score was created with the specificity of 91% and sensitivity of 68% for detecting the presence of ACR in the EMB sample. Conclusion: We identified a set of microRNAs altered in endomyocardial biopsies during ACR and using their relative levels we created a diagnostic score that can be used for ACR diagnosis.
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spelling pubmed-69124722020-01-02 Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing Nováková, Tereza Macháčková, Táňa Novák, Jan Hude, Petr Godava, Július Žampachová, Víta Oppelt, Jan Zlámal, Filip Němec, Petr Bedáňová, Helena Slabý, Ondřej Bienertová-Vašků, Julie Špinarová, Lenka Krejčí, Jan Cells Article Introduction: Acute cellular rejection (ACR) of heart allografts represents the most common reason for graft failure. Endomyocardial biopsies (EMB) are still subject to substantial interobserver variability. Novel biomarkers enabling precise ACR diagnostics may decrease interobserver variability. We aimed to identify a specific subset of microRNAs reflecting the presence of ACR. Patients and Methods: Monocentric retrospective study. A total of 38 patients with the anamnesis of ACR were identified and for each patient three consecutive samples of EMB (with, prior and after ACR) were collected. Sixteen trios were used for next-generation sequencing (exploratory cohort); the resting 22 trios were used for validation with qRT-PCR (validation cohort). Statistical analysis was performed using R software. Results: The analysis of the exploration cohort provided the total of 11 miRNAs that were altered during ACR, the three of which (miR-144, miR-589 and miR-182) were further validated in the validation cohort. Using the levels of all 11 miRNAs and principal component analysis, an ACR score was created with the specificity of 91% and sensitivity of 68% for detecting the presence of ACR in the EMB sample. Conclusion: We identified a set of microRNAs altered in endomyocardial biopsies during ACR and using their relative levels we created a diagnostic score that can be used for ACR diagnosis. MDPI 2019-11-06 /pmc/articles/PMC6912472/ /pubmed/31698874 http://dx.doi.org/10.3390/cells8111400 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nováková, Tereza
Macháčková, Táňa
Novák, Jan
Hude, Petr
Godava, Július
Žampachová, Víta
Oppelt, Jan
Zlámal, Filip
Němec, Petr
Bedáňová, Helena
Slabý, Ondřej
Bienertová-Vašků, Julie
Špinarová, Lenka
Krejčí, Jan
Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing
title Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing
title_full Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing
title_fullStr Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing
title_full_unstemmed Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing
title_short Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing
title_sort identification of a diagnostic set of endomyocardial biopsy micrornas for acute cellular rejection diagnostics in patients after heart transplantation using next-generation sequencing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912472/
https://www.ncbi.nlm.nih.gov/pubmed/31698874
http://dx.doi.org/10.3390/cells8111400
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