Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing
Introduction:<b> </b>Acute cellular rejection (ACR) of heart allografts represents the most common reason for graft failure. Endomyocardial biopsies (EMB) are still subject to substantial interobserver variability. Novel biomarkers enabling precise ACR diagnostics may decrease interobser...
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MDPI AG
2019-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/8/11/1400 |
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| author | Tereza Nováková Táňa Macháčková Jan Novák Petr Hude Július Godava Víta Žampachová Jan Oppelt Filip Zlámal Petr Němec Helena Bedáňová Ondřej Slabý Julie Bienertová-Vašků Lenka Špinarová Jan Krejčí |
| author_facet | Tereza Nováková Táňa Macháčková Jan Novák Petr Hude Július Godava Víta Žampachová Jan Oppelt Filip Zlámal Petr Němec Helena Bedáňová Ondřej Slabý Julie Bienertová-Vašků Lenka Špinarová Jan Krejčí |
| author_sort | Tereza Nováková |
| collection | DOAJ |
| description | Introduction:<b> </b>Acute cellular rejection (ACR) of heart allografts represents the most common reason for graft failure. Endomyocardial biopsies (EMB) are still subject to substantial interobserver variability. Novel biomarkers enabling precise ACR diagnostics may decrease interobserver variability. We aimed to identify a specific subset of microRNAs reflecting the presence of ACR. Patients and Methods:<b> </b>Monocentric retrospective study. A total of 38 patients with the anamnesis of ACR were identified and for each patient three consecutive samples of EMB (with, prior and after ACR) were collected. Sixteen trios were used for next-generation sequencing (exploratory cohort); the resting 22 trios were used for validation with qRT-PCR (validation cohort). Statistical analysis was performed using R software. Results: The analysis of the exploration cohort provided the total of 11 miRNAs that were altered during ACR, the three of which (miR-144, miR-589 and miR-182) were further validated in the validation cohort. Using the levels of all 11 miRNAs and principal component analysis, an ACR score was created with the specificity of 91% and sensitivity of 68% for detecting the presence of ACR in the EMB sample. Conclusion:<b> </b>We identified a set of microRNAs altered in endomyocardial biopsies during ACR and using their relative levels we created a diagnostic score that can be used for ACR diagnosis. |
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| spelling | doaj.art-66345efdeebe41bd954563caef31b2062023-09-02T02:22:03ZengMDPI AGCells2073-44092019-11-01811140010.3390/cells8111400cells8111400Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation SequencingTereza Nováková0Táňa Macháčková1Jan Novák2Petr Hude3Július Godava4Víta Žampachová5Jan Oppelt6Filip Zlámal7Petr Němec8Helena Bedáňová9Ondřej Slabý10Julie Bienertová-Vašků11Lenka Špinarová12Jan Krejčí13Department of Cardiovascular Diseases, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, Pekařská 53, 65691Brno, Czech RepublicCentral European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno, Czech RepublicCentral European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno, Czech RepublicDepartment of Cardiovascular Diseases, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, Pekařská 53, 65691Brno, Czech RepublicDepartment of Cardiovascular Diseases, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, Pekařská 53, 65691Brno, Czech RepublicDepartment of Pathology, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, Pekařská 53, 65691 Brno, Czech RepublicCentral European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno, Czech RepublicDepartment of Pathological Physiology, Masaryk University, Kamenice 5, 62500 Brno, Czech RepublicCentre of Cardiovascular Surgery and Organ Transplantation, Pekařská 53, 65691 Brno, Czech RepublicCentre of Cardiovascular Surgery and Organ Transplantation, Pekařská 53, 65691 Brno, Czech RepublicCentral European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno, Czech RepublicDepartment of Pathological Physiology, Masaryk University, Kamenice 5, 62500 Brno, Czech RepublicDepartment of Cardiovascular Diseases, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, Pekařská 53, 65691Brno, Czech RepublicDepartment of Cardiovascular Diseases, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, Pekařská 53, 65691Brno, Czech RepublicIntroduction:<b> </b>Acute cellular rejection (ACR) of heart allografts represents the most common reason for graft failure. Endomyocardial biopsies (EMB) are still subject to substantial interobserver variability. Novel biomarkers enabling precise ACR diagnostics may decrease interobserver variability. We aimed to identify a specific subset of microRNAs reflecting the presence of ACR. Patients and Methods:<b> </b>Monocentric retrospective study. A total of 38 patients with the anamnesis of ACR were identified and for each patient three consecutive samples of EMB (with, prior and after ACR) were collected. Sixteen trios were used for next-generation sequencing (exploratory cohort); the resting 22 trios were used for validation with qRT-PCR (validation cohort). Statistical analysis was performed using R software. Results: The analysis of the exploration cohort provided the total of 11 miRNAs that were altered during ACR, the three of which (miR-144, miR-589 and miR-182) were further validated in the validation cohort. Using the levels of all 11 miRNAs and principal component analysis, an ACR score was created with the specificity of 91% and sensitivity of 68% for detecting the presence of ACR in the EMB sample. Conclusion:<b> </b>We identified a set of microRNAs altered in endomyocardial biopsies during ACR and using their relative levels we created a diagnostic score that can be used for ACR diagnosis.https://www.mdpi.com/2073-4409/8/11/1400micrornaendomyocardial biopsyheart transplantationacute cellular rejectiondiagnostics |
| spellingShingle | Tereza Nováková Táňa Macháčková Jan Novák Petr Hude Július Godava Víta Žampachová Jan Oppelt Filip Zlámal Petr Němec Helena Bedáňová Ondřej Slabý Julie Bienertová-Vašků Lenka Špinarová Jan Krejčí Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing Cells microrna endomyocardial biopsy heart transplantation acute cellular rejection diagnostics |
| title | Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing |
| title_full | Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing |
| title_fullStr | Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing |
| title_full_unstemmed | Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing |
| title_short | Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing |
| title_sort | identification of a diagnostic set of endomyocardial biopsy micrornas for acute cellular rejection diagnostics in patients after heart transplantation using next generation sequencing |
| topic | microrna endomyocardial biopsy heart transplantation acute cellular rejection diagnostics |
| url | https://www.mdpi.com/2073-4409/8/11/1400 |
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