Circulating miR-181a-5p as a new biomarker for acute cellular rejection in heart transplantation
Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved..
BACKGROUND: Acute cellular rejection (ACR) is a major complication in heart transplantation (HTx). Endomyocardial biopsy is the reference method for early detection of ACR, but a new non-invasive approach is needed. Tentative candidates could be circulating microRNAs. This study aimed to discover and validate microRNAs in serum for ACR detection after HTx.
METHODS: This prospective, observational, single-center study included 121 HTx patients. ACR was graded according to International Society of Heart and Lung Transplantation classification (0R-3R). First, in the discovery phase, microRNA expression profile was carried out in serum samples from patients at pre-rejection, during, and post-rejection time (0RS1 → 2RS2` → 0RS3). Relative expression (2-∆Cq) of 179 microRNAs per sample was analyzed by reverse transcription quantitative polymerase chain reaction. Second, a microRNA with a significant rise and fall pattern during ACR was selected for the next validation phase, where it was analyzed (reverse transcription quantitative polymerase chain reaction) in serum samples from 2 groups of patients: the no-ACR group (0R grade) and the ACR group (≥2R grade). Finally, a sensitivity analysis (receiver operating characteristic curve) was done to assess microRNA accuracy for ACR detection in HTx.
RESULTS: A total of 21 ACR episodes (0RS1 → 2RS2 → 0RS3) with their respective serum samples (n = 63) were included in the discovery phase. Among the 179 microRNAs analyzed, only miR-181a-5p met the rise and fall criteria. In the validation phase, miR-181a-5p relative expression (2-∆Cq) in the ACR group (n = 45) was significantly overexpressed (p < 0.0001) vs the no-ACR group (n = 45). miR-181a-5p showed an area under the curve of 0.804 (95% confidence interval: 0.707-0.880); sensitivity and specificity of 78% and 76%, respectively; and a negative predicted value of 98%.
CONCLUSIONS: miR-185a-5p in serum is a candidate as a non-invasive ACR biomarker (area under the curve = 0.80 and negative predicted value = 98%). Thus, this biomarker could reduce the need for endomyocardial biopsies and the associated risks and costs of this invasive procedure.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:39 |
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| Enthalten in: |
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation - 39(2020), 10 vom: 31. Okt., Seite 1100-1108 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Constanso-Conde, Ignacio [VerfasserIn] |
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| Links: |
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| Themen: |
Acute rejection |
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| Anmerkungen: |
Date Completed 31.08.2021 Date Revised 31.08.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.healun.2020.05.018 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31231616X |
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| 100 | 1 | |a Constanso-Conde, Ignacio |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Circulating miR-181a-5p as a new biomarker for acute cellular rejection in heart transplantation |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 31.08.2021 | ||
| 500 | |a Date Revised 31.08.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Acute cellular rejection (ACR) is a major complication in heart transplantation (HTx). Endomyocardial biopsy is the reference method for early detection of ACR, but a new non-invasive approach is needed. Tentative candidates could be circulating microRNAs. This study aimed to discover and validate microRNAs in serum for ACR detection after HTx | ||
| 520 | |a METHODS: This prospective, observational, single-center study included 121 HTx patients. ACR was graded according to International Society of Heart and Lung Transplantation classification (0R-3R). First, in the discovery phase, microRNA expression profile was carried out in serum samples from patients at pre-rejection, during, and post-rejection time (0RS1 → 2RS2` → 0RS3). Relative expression (2-∆Cq) of 179 microRNAs per sample was analyzed by reverse transcription quantitative polymerase chain reaction. Second, a microRNA with a significant rise and fall pattern during ACR was selected for the next validation phase, where it was analyzed (reverse transcription quantitative polymerase chain reaction) in serum samples from 2 groups of patients: the no-ACR group (0R grade) and the ACR group (≥2R grade). Finally, a sensitivity analysis (receiver operating characteristic curve) was done to assess microRNA accuracy for ACR detection in HTx | ||
| 520 | |a RESULTS: A total of 21 ACR episodes (0RS1 → 2RS2 → 0RS3) with their respective serum samples (n = 63) were included in the discovery phase. Among the 179 microRNAs analyzed, only miR-181a-5p met the rise and fall criteria. In the validation phase, miR-181a-5p relative expression (2-∆Cq) in the ACR group (n = 45) was significantly overexpressed (p < 0.0001) vs the no-ACR group (n = 45). miR-181a-5p showed an area under the curve of 0.804 (95% confidence interval: 0.707-0.880); sensitivity and specificity of 78% and 76%, respectively; and a negative predicted value of 98% | ||
| 520 | |a CONCLUSIONS: miR-185a-5p in serum is a candidate as a non-invasive ACR biomarker (area under the curve = 0.80 and negative predicted value = 98%). Thus, this biomarker could reduce the need for endomyocardial biopsies and the associated risks and costs of this invasive procedure | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a acute rejection | |
| 650 | 4 | |a biomarker | |
| 650 | 4 | |a heart transplantation | |
| 650 | 4 | |a miR-181a-5p | |
| 650 | 4 | |a microRNA | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a MIrn181 microRNA, human |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 700 | 1 | |a Hermida-Prieto, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Barge-Caballero, Eduardo |e verfasserin |4 aut | |
| 700 | 1 | |a Núñez, Lucía |e verfasserin |4 aut | |
| 700 | 1 | |a Pombo-Otero, Jorge |e verfasserin |4 aut | |
| 700 | 1 | |a Suárez-Fuentetaja, Natalia |e verfasserin |4 aut | |
| 700 | 1 | |a Paniagua-Martín, María Jesús |e verfasserin |4 aut | |
| 700 | 1 | |a Barge-Caballero, Gonzalo |e verfasserin |4 aut | |
| 700 | 1 | |a Couto-Mallón, David |e verfasserin |4 aut | |
| 700 | 1 | |a Pan-Lizcano, Ricardo |e verfasserin |4 aut | |
| 700 | 1 | |a Vázquez-Rodríguez, José Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Crespo-Leiro, María Generosa |e verfasserin |4 aut | |
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