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Biomarker discovery in cardiac allograft vasculopathy using targeted aptamer proteomics
Author(s) -
Almufleh Aws,
Zhang Liyong,
Mielniczuk Lisa M.,
Stadnick Ellamae,
Davies Ross A.,
Du Qiujiang,
Rayner Katey,
Liu Peter P.,
Chih Sharon
Publication year - 2020
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.13765
Subject(s) - medicine , biomarker , biomarker discovery , heart transplantation , receiver operating characteristic , area under the curve , transplantation , cardiology , oncology , proteomics , pathology , bioinformatics , gastroenterology , biology , gene , biochemistry
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: CAV 1‐2 (mild‐moderate CAV), CAV 3 (severe CAV), and CAV 0 (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.