Feasibility and Potential of Transcriptomic Analysis Using the NanoString nCounter Technology to Aid the Classification of Rejection in Kidney Transplant Biopsies
Transplantation, vol. 107, pp. 903–912
Abstract
BACKGROUND: Transcriptome analysis could be an additional diagnostic parameter in diagnosing kidney transplant (KTx) rejection. Here, we assessed feasibility and potential of NanoString nCounter analysis of KTx biopsies to aid the classification of rejection in clinical practice using both the Banff-Human Organ Transplant (B-HOT) panel and a customized antibody-mediated rejection (AMR)-specific NanoString nCounter Elements (Elements) panel. Additionally, we explored the potential for the classification of KTx rejection building and testing a classifier within our dataset. METHODS: Ninety-six formalin-fixed paraffin-embedded KTx biopsies were retrieved from the archives of the ErasmusMC Rotterdam and the University Hospital Cologne. Biopsies with AMR, borderline or T cell-mediated rejections (BLorTCMR), and no rejection were compared using the B-HOT and Elements panels. RESULTS: High correlation between gene expression levels was found when comparing the 2 chemistries pairwise (r = 0.76-0.88). Differential gene expression (false discovery rate; P < 0.05) was identified in biopsies diagnosed with AMR (B-HOT: 294; Elements: 76) and BLorTCMR (B-HOT: 353; Elements: 57) compared with no rejection. Using the most predictive genes from the B-HOT analysis and the Element analysis, 2 least absolute shrinkage and selection operators-based regression models to classify biopsies as AMR versus no AMR (BLorTCMR or no rejection) were developed achieving an receiver-operating-characteristic curve of 0.994 and 0.894, sensitivity of 0.821 and 0.480, and specificity of 1.00 and 0.979, respectively, during cross-validation. CONCLUSIONS: Transcriptomic analysis is feasible on KTx biopsies previously used for diagnostic purposes. The B-HOT panel has the potential to differentiate AMR from BLorTCMR or no rejection and could prove valuable in aiding kidney transplant rejection classification.
Authors 24
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Hilal Varol corresponding
Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Pathology, University Medical Center Rotterdam, Rotterdam, The Netherlands
Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
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University of Cologne · University Hospital Cologne
Affiliation as printed
Institute of Medical Statistics and Computational Biology, University Hospital of Cologne, Cologne, Germany
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Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Pathology, Clinical Bioinformatics Unit, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Surgery, Division of HPB & Transplant Surgery, University Medical Center Rotterdam, Rotterdam, The Netherlands
Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Affiliation as printed
Cologne Merheim Medical Center, Cologne General Hospital, Cologne, Germany
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Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Internal Medicine, Division of Nephrology and Transplantation, University Medical Center Rotterdam, Rotterdam, The Netherlands
Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Pathology, Clinical Bioinformatics Unit, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Surgery, Division of HPB & Transplant Surgery, University Medical Center Rotterdam, Rotterdam, The Netherlands
Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Affiliation as printed
Department of Pathology, University Medical Center Rotterdam, Rotterdam, The Netherlands
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University of Cologne · University Hospital Cologne
Affiliation as printed
Department of General Visceral Cancer and Transplant Surgery Transplant Center Cologne, University of Cologne Faculty of Medicine and University Hospital of Cologne, Cologne, Germany
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Affiliation as printed
Cologne Merheim Medical Center, Cologne General Hospital, Cologne, Germany
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Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Internal Medicine, Division of Nephrology and Transplantation, University Medical Center Rotterdam, Rotterdam, The Netherlands
Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Affiliation as printed
Department of Pathology, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Erasmus MC · Erasmus University Rotterdam
Affiliation as printed
Department of Pathology, Clinical Bioinformatics Unit, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Pathology, Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, Rotterdam, The Netherlands
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University of Cologne · University Hospital Cologne
Affiliation as printed
Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
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Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Surgery, Division of HPB & Transplant Surgery, University Medical Center Rotterdam, Rotterdam, The Netherlands
Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Erasmus MC · Erasmus University Rotterdam
Affiliation as printed
Department of Pathology, Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, Rotterdam, The Netherlands
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Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Internal Medicine, Division of Nephrology and Transplantation, University Medical Center Rotterdam, Rotterdam, The Netherlands
Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Affiliation as printed
Department of Pathology, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Erasmus MC · Amsterdam UMC Location University of Amsterdam
Affiliation as printed
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
Department of Pathology, University Medical Center Rotterdam, Rotterdam, The Netherlands
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University of Cologne · University Hospital Cologne
Affiliation as printed
Department of General Visceral Cancer and Transplant Surgery Transplant Center Cologne, University of Cologne Faculty of Medicine and University Hospital of Cologne, Cologne, Germany
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Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Pathology, Clinical Bioinformatics Unit, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Pathology, University Medical Center Rotterdam, Rotterdam, The Netherlands
Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
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University of Bonn · Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Internal Medicine, Faculty of Medicine, University Bonn, Bonn, Germany
Department of Pathology, University Medical Center Rotterdam, Rotterdam, The Netherlands
Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
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University of Cologne · Erasmus MC · University Hospital Cologne
Affiliation as printed
Institute of Pathology, University Hospital of Cologne, Cologne, Germany
Department of Pathology, University Medical Center Rotterdam, Rotterdam, The Netherlands
Institute of Medical Statistics and Computational Biology, University Hospital of Cologne, Cologne, Germany
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Erasmus MC · Erasmus MC Transplant Institute · RWTH Aachen University
Affiliation as printed
Department of Pathology, University Medical Center Rotterdam, Rotterdam, The Netherlands
Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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