Biomarker discovery in cardiac allograft vasculopathy using targeted aptamer proteomics |
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Authors: | Aws Almufleh Liyong Zhang Lisa M. Mielniczuk Ellamae Stadnick Ross A. Davies Qiujiang Du Katey Rayner Peter P. Liu Sharon Chih |
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Affiliation: | 1. Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada;2. Cardiac function laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada;3. Cardiometabolic microRNA Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada;4. Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada Cardiac function laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada Department of Medicine and Cellular & Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada |
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Abstract: | Cardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation. Non-invasive evaluation is challenging, and currently, there is no validated biomarker for CAV diagnosis or prognostication. To identify potential candidate CAV biomarkers, we utilized the Slow Off-rate Modified Aptamer (SOMAscan) assay, which evaluates over 1000 serum proteins, including many relevant to biological pathways in CAV. We evaluated three heart transplant patient groups according to angiographic ISHLT CAV grade: CAV1-2 (mild-moderate CAV), CAV3 (severe CAV), and CAV0 (normal control). SOMAscan assays were performed and proteins quantitated. Comparisons of proteins between study groups were performed using one-way ANOVA (false discovery rate q-value < 0.10). Thirty-one patients (12 mild-moderate CAV, 9 severe CAV, 10 controls) were included: 81% male, median age 57 years and median 1.1 years post-transplant. Compared to controls, patients with mild-moderate CAV had similar characteristics, while patients with severe CAV had longer time from transplant and increased allosensitization. Statistical/bioinformatics analysis identified 14 novel biomarkers for CAV, including 4 specific for mild-moderate CAV. These proteins demonstrated important actions including apoptosis, inflammation, and platelet/coagulation activation. Upon preliminary receiver operating characteristics curve analysis, our protein biomarkers showed moderate-to-high discriminative ability for CAV (area under curve: 0.72 to 0.94). These candidate biomarkers are being validated in prospective studies. |
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Keywords: | aptamer proteomic profiling cardiac allograft vasculopathy serum biomarkers |
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