Circulating miR-181a-5p as a New Biomarker for Acute Cellular Rejection in Heart Transplantation
| Autor: | Eduardo Barge-Caballero, Gonzalo Barge-Caballero, María J. Paniagua-Martín, José Manuel Vázquez-Rodríguez, Lucía Núñez, María G. Crespo-Leiro, Manuel Hermida-Prieto, Ignacio Constanso-Conde, David Couto-Mallón, Jorge Pombo-Otero, Natalia Suárez-Fuentetaja, Ricardo Pan-Lizcano |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Pulmonary and Respiratory Medicine Oncology Adult Graft Rejection Male medicine.medical_specialty medicine.medical_treatment miR-181a-5p 030204 cardiovascular system & hematology Heart transplantation 03 medical and health sciences 0302 clinical medicine Internal medicine microRNA Medicine Lung transplantation Humans Prospective Studies Transplantation Receiver operating characteristic business.industry MicroRNA MicroRNA Expression Profile Biomarker Middle Aged Prognosis Circulating MicroRNA MicroRNAs 030104 developmental biology Real-time polymerase chain reaction ROC Curve Biomarker (medicine) Heart Transplantation Acute rejection Surgery Female Cardiology and Cardiovascular Medicine business Biomarkers Follow-Up Studies |
| Zdroj: | RUC. Repositorio da Universidade da Coruña Universitat Oberta de Catalunya (UOC) RUC: Repositorio da Universidade da Coruña Universidade da Coruña (UDC) |
| Popis: | [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 (0RS1 → 2RS2 → 0RS3). Relative expression (2-ΔCq) 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-ΔCq) 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%. This study received financial support from Instituto de Salud Carlos III (PI15/02224), is part of the research activities of the Centro de investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), and was cofinanced with FEDER Funds |
| Databáze: | OpenAIRE |
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