The microRNA Expression Profile in Donation after Cardiac Death (DCD) Livers and Its Ability to Identify Primary Non Function

Donation after cardiac death (DCD) livers are marginal organs for transplant and their use is associated with a higher risk of primary non function (PNF) or early graft dysfunction (EGD). The aim was to determine if microRNA (miRNA) was able to discriminate between DCD livers of varying clinical out...

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Veröffentlicht in:PloS one 2015-05, Vol.10 (5), p.e0127073-e0127073
Hauptverfasser: Khorsandi, Shirin Elizabeth, Quaglia, Alberto, Salehi, Siamak, Jassem, Wayel, Vilca-Melendez, Hector, Prachalias, Andreas, Srinivasan, Parthi, Heaton, Nigel
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container_title PloS one
container_volume 10
creator Khorsandi, Shirin Elizabeth
Quaglia, Alberto
Salehi, Siamak
Jassem, Wayel
Vilca-Melendez, Hector
Prachalias, Andreas
Srinivasan, Parthi
Heaton, Nigel
description Donation after cardiac death (DCD) livers are marginal organs for transplant and their use is associated with a higher risk of primary non function (PNF) or early graft dysfunction (EGD). The aim was to determine if microRNA (miRNA) was able to discriminate between DCD livers of varying clinical outcome. DCD groups were categorized as PNF retransplanted within a week (n=7), good functional outcome (n=7) peak aspartate transaminase (AST) ≤ 1000 IU/L and EGD (n=9) peak AST ≥ 2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru-cut liver biopsies. High throughput expression analysis was performed using miRNA arrays. Bioinformatics for expression data analysis was performed and validated with real time quantitative PCR (RT-qPCR). The function of miRNA of interest was investigated using computational biology prediction algorithms. From the array analysis 16 miRNAs were identified as significantly different (p
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The aim was to determine if microRNA (miRNA) was able to discriminate between DCD livers of varying clinical outcome. DCD groups were categorized as PNF retransplanted within a week (n=7), good functional outcome (n=7) peak aspartate transaminase (AST) ≤ 1000 IU/L and EGD (n=9) peak AST ≥ 2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru-cut liver biopsies. High throughput expression analysis was performed using miRNA arrays. Bioinformatics for expression data analysis was performed and validated with real time quantitative PCR (RT-qPCR). The function of miRNA of interest was investigated using computational biology prediction algorithms. From the array analysis 16 miRNAs were identified as significantly different (p&lt;0.05). On RT-qPCR miR-155 and miR-940 had the highest expression across all three DCD clinical groups. Only one miRNA, miR-22, was validated with marginal significance, to have differential expression between the three groups (p=0.049). From computational biology miR-22 was predicted to affect signalling pathways that impact protein turnover, metabolism and apoptosis/cell cycle. 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The aim was to determine if microRNA (miRNA) was able to discriminate between DCD livers of varying clinical outcome. DCD groups were categorized as PNF retransplanted within a week (n=7), good functional outcome (n=7) peak aspartate transaminase (AST) ≤ 1000 IU/L and EGD (n=9) peak AST ≥ 2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru-cut liver biopsies. High throughput expression analysis was performed using miRNA arrays. Bioinformatics for expression data analysis was performed and validated with real time quantitative PCR (RT-qPCR). The function of miRNA of interest was investigated using computational biology prediction algorithms. From the array analysis 16 miRNAs were identified as significantly different (p&lt;0.05). On RT-qPCR miR-155 and miR-940 had the highest expression across all three DCD clinical groups. Only one miRNA, miR-22, was validated with marginal significance, to have differential expression between the three groups (p=0.049). From computational biology miR-22 was predicted to affect signalling pathways that impact protein turnover, metabolism and apoptosis/cell cycle. In conclusion, microRNA expression patterns have a low diagnostic potential clinically in discriminating DCD liver quality and outcome.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25978529</pmid><doi>10.1371/journal.pone.0127073</doi><oa>free_for_read</oa></addata></record>
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subjects Adult
Algorithms
Analysis
Apoptosis
Arrays
Aspartate Aminotransferases - blood
Aspartate transaminase
Bioinformatics
Biology
Biopsy
Care and treatment
Cell cycle
Complications and side effects
Computation
Computer applications
Data analysis
Data processing
Death
Diagnostic systems
Gene expression
Genomics
Heart diseases
Humans
Hypoglycemia
Hypoxia
Influence
Ischemia
Liver
Liver - metabolism
Liver Transplantation - methods
Liver transplants
Metabolism
MicroRNA
MicroRNAs
MicroRNAs - genetics
Middle Aged
miRNA
Organs
Perfusion
Predictions
Protein turnover
Ribonucleic acid
RNA
Rodents
Signal transduction
Signaling
Studies
Tissue and Organ Procurement - methods
Tissue Donors
Transaminase
Transcriptome - genetics
Transplants & implants
title The microRNA Expression Profile in Donation after Cardiac Death (DCD) Livers and Its Ability to Identify Primary Non Function
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