title: The microRNA Expression Profile in Donation after Cardiac Death (DCD) Livers and Its Ability to Identify Primary Non Function.
abstract: 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<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.
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors.forename: Shirin Elizabeth
authors.initials: SE
authors.lastname: Khorsandi
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors.forename: Alberto
authors.initials: A
authors.lastname: Quaglia
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors.forename: Siamak
authors.initials: S
authors.lastname: Salehi
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors.forename: Wayel
authors.initials: W
authors.lastname: Jassem
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors.forename: Hector
authors.initials: H
authors.lastname: Vilca-Melendez
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors.forename: Andreas
authors.initials: A
authors.lastname: Prachalias
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors.forename: Parthi
authors.initials: P
authors.lastname: Srinivasan
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors.forename: Nigel
authors.initials: N
authors.lastname: Heaton
mesh_terms: D000328:Adult; D001219:Aspartate Aminotransferases / Q000097:blood; D003643:Death; D006801:Humans; D008099:Liver / Q000378:metabolism*; D016031:Liver Transplantation / Q000379:methods; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D014019:Tissue Donors; D009927:Tissue and Organ Procurement / Q000379:methods; D059467:Transcriptome / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D001219:Aspartate Aminotransferases