Lorena Pérez-Carrillo, Irene González-Torrent, Isaac Giménez-Escamilla, Marta Delgado-Arija, Carlota Benedicto, Manuel Portolés, Estefanía Tarazón, Esther Roselló-Lletí
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引用次数: 0
Abstract
Background: Liquid biopsy offers a potential alternative to decrease or eliminate endomyocardial biopsy (EMB) for diagnosing allograft rejection. piRNAs are novel and promising disease biomarkers for their intrinsic characteristics such as stability in body fluids; however, their role in allograft rejection remains unexplored.
Methods: A training set based on small RNA sequencing technology was performed to identify piRNAs in endomyocardial tissue (n=8) and serum samples (n=40) from patients following heart transplantation. A validation set of the potential piRNAs identified in the training study was conducted in an independent larger cohort for the detection of acute cellular rejection (ACR, n=105) and antibody-mediated rejection (AMR, n=61).
Results: We identified 20292 piRNAs in endomyocardial tissue and 24602 piRNAs in serum samples from patients following heart transplantation. We identified seven piRNAs with a coincident expression profile in both types of samples and potential capacity for the non-invasive detection of cardiac rejection. Validation in a large independent cohort demonstrated that a panel of these piRNAs showed excellent performance for detecting grade ≥2R ACR (AUC=0.819; p<0.0001) and grade 1R ACR (AUC=0.721; p=0.001). Furthermore, our piRNA panel showed a potential discrimination ability of pAMR2 (AUC=0.967; p<0.0001).
Conclusions: To the best of knowledge, this study is the first to report the presence of piRNAs in both endomyocardial tissue and serum samples of patients after heart transplant, including their association with allograft rejection events. We propose a novel piRNA panel for the detection of cardiac allograft rejection.
期刊介绍:
The Journal of Heart and Lung Transplantation, the official publication of the International Society for Heart and Lung Transplantation, brings readers essential scholarly and timely information in the field of cardio-pulmonary transplantation, mechanical and biological support of the failing heart, advanced lung disease (including pulmonary vascular disease) and cell replacement therapy. Importantly, the journal also serves as a medium of communication of pre-clinical sciences in all these rapidly expanding areas.