Circulating miR-181a-5p as a new biomarker for acute cellular rejection in heart transplantation

JOURNAL OF HEART AND LUNG TRANSPLANTATION

卷:39

Article

Constanso-Conde, Ignacio¹  Hermida-Prieto, Manuel¹  Barge-Caballero, Eduardo²  Nunez, Lucia¹  Pombo-Otero, Jorge³  Suarez-Fuentetaja, Natalia¹  Jesus Paniagua-Martin, Maria²  Barge-Caballero, Gonzalo²  Couto-Mallon, David²  Pan-Lizcano, Ricardo¹  Manuel Vazquez-Rodriguez, Jose²  Generosa Crespo-Leiro, Maria² 

[1] Univ Coruna UDC, Inst Invest Biomed A Coruna INIBIC, Grp Invest Cardiol, Complexo Hosp Univ A Coruna CHUAC,SERGAS, La Coruna, Spain

[2] Univ Coruna UDC, Complexo Hosp Univ A Coruna CHUAC, Inst Invest Biomed A Coruna INIBIC, CIBERCV,SERGAS,Serv Cardiol, La Coruna, Spain

[3] Complexo Hosp Univ A Coruna CHUAC SERGAS, Serv Anat Patol, La Coruna, Spain

关键词: heart transplantation;    acute rejection;    microRNA;    miR-181a-5p;    biornarker;   

DOI  :  10.1016/j.healun.2020.05.018

来源: Elsevier

【 摘 要 】

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 (OR-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 (ORS1 -> 2R(S2), -> ORS3). Relative expression (2(-Delta)(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 (OR 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 (ORS1 -> 2R(S2 )-> ORS3) with their respective serum samples (n = 63) were included in the discovery phase. Among the 179 microRNAs analyzed, only miR181a-5p met the rise and fall criteria. In the validation phase, miR-181a-5p relative expression (2(-Delta 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. (C) 2020 International Society for Heart and Lung Transplantation. All rights reserved.

【 授权许可】

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