Circulating miR-181a-5p as a new biomarker for acute cellular rejection in heart transplantation.
J Heart Lung Transplant
; 39(10): 1100-1108, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32654912
ABSTRACT
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 (0RS1â¯ââ¯2RS2`â¯ââ¯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 (0RS1â¯ââ¯2RS2â¯ââ¯0RS3) with their respective serum samples (nâ¯=â¯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 (nâ¯=â¯45) was significantly overexpressed (p < 0.0001) vs the no-ACR group (nâ¯=â¯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 curveâ¯=â¯0.80 and negative predicted valueâ¯=â¯98%). Thus, this biomarker could reduce the need for endomyocardial biopsies and the associated risks and costs of this invasive procedure.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transplante de Coração
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MicroRNAs
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Rejeição de Enxerto
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article