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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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<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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0127073</identifier><identifier>PMID: 25978529</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0127073-e0127073</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Khorsandi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Khorsandi et al 2015 Khorsandi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c651t-15e4e256cda612e2e6e58ae88d67804d038c99acbff00ceb0560aa059da304d23</citedby><cites>FETCH-LOGICAL-c651t-15e4e256cda612e2e6e58ae88d67804d038c99acbff00ceb0560aa059da304d23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433116/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433116/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25978529$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khorsandi, Shirin Elizabeth</creatorcontrib><creatorcontrib>Quaglia, Alberto</creatorcontrib><creatorcontrib>Salehi, Siamak</creatorcontrib><creatorcontrib>Jassem, Wayel</creatorcontrib><creatorcontrib>Vilca-Melendez, Hector</creatorcontrib><creatorcontrib>Prachalias, Andreas</creatorcontrib><creatorcontrib>Srinivasan, Parthi</creatorcontrib><creatorcontrib>Heaton, Nigel</creatorcontrib><title>The microRNA Expression Profile in Donation after Cardiac Death (DCD) Livers and Its Ability to Identify Primary Non Function</title><title>PloS one</title><addtitle>PLoS One</addtitle><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<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.</description><subject>Adult</subject><subject>Algorithms</subject><subject>Analysis</subject><subject>Apoptosis</subject><subject>Arrays</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Aspartate transaminase</subject><subject>Bioinformatics</subject><subject>Biology</subject><subject>Biopsy</subject><subject>Care and treatment</subject><subject>Cell cycle</subject><subject>Complications and side effects</subject><subject>Computation</subject><subject>Computer applications</subject><subject>Data analysis</subject><subject>Data processing</subject><subject>Death</subject><subject>Diagnostic systems</subject><subject>Gene expression</subject><subject>Genomics</subject><subject>Heart diseases</subject><subject>Humans</subject><subject>Hypoglycemia</subject><subject>Hypoxia</subject><subject>Influence</subject><subject>Ischemia</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Liver Transplantation - methods</subject><subject>Liver transplants</subject><subject>Metabolism</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Organs</subject><subject>Perfusion</subject><subject>Predictions</subject><subject>Protein turnover</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Rodents</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Studies</subject><subject>Tissue and Organ Procurement - methods</subject><subject>Tissue Donors</subject><subject>Transaminase</subject><subject>Transcriptome - genetics</subject><subject>Transplants & implants</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptkl1v0zAUhiMEYmPwDxBYQkLjosVfcZIbpKrdoFI1EBrX1qlz0rpK485OJnrBf8dZs6lFXNnyec9zPvwmyVtGx0xk7PPGdb6BerxzDY4p4xnNxLPknBWCjxSn4vnR_Sx5FcKG0lTkSr1MznhaZHnKi_Pkz-0aydYa737eTMjV753HEKxryA_vKlsjsQ2ZuQba_g2qFj2Zgi8tGDJDaNfkcjadfSILe48-EGhKMm8DmSxtbds9aR2Zl9i0ttpHoN2C35ObCLruGtMTXycvKqgDvhnOi-TX9dXt9Nto8f3rfDpZjIxKWTtiKUrkqTIlKMaRo8I0B8zzUmU5lSUVuSkKMMuqotTgkqaKAtC0KEHEMBcXyfsDd1e7oIfNBc1UzmghlaRRMT8oSgcbvTv0qh1Y_fDg_EqDb62pUUcyUBpr8iKThRDLMq2WhkqoaKFY0bO-DNW65RZLExfgoT6BnkYau9Yrd6-lFIIxFQGXA8C7uw5Dq7c2GKxraNB1D31zTrNUZlH64R_p_6cbVCuIA9imcrGu6aF6IgVnVArFourjkWqNULfr4Oqu_6lwKpQHYbRNCB6rp9kY1b05H5vQvTn1YM6Y9u54L09Jj24UfwERAt_a</recordid><startdate>20150515</startdate><enddate>20150515</enddate><creator>Khorsandi, Shirin Elizabeth</creator><creator>Quaglia, Alberto</creator><creator>Salehi, Siamak</creator><creator>Jassem, Wayel</creator><creator>Vilca-Melendez, Hector</creator><creator>Prachalias, Andreas</creator><creator>Srinivasan, Parthi</creator><creator>Heaton, Nigel</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150515</creationdate><title>The microRNA Expression Profile in Donation after Cardiac Death (DCD) Livers and Its Ability to Identify Primary Non Function</title><author>Khorsandi, Shirin Elizabeth ; Quaglia, Alberto ; Salehi, Siamak ; Jassem, Wayel ; Vilca-Melendez, Hector ; Prachalias, Andreas ; Srinivasan, Parthi ; Heaton, Nigel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c651t-15e4e256cda612e2e6e58ae88d67804d038c99acbff00ceb0560aa059da304d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Algorithms</topic><topic>Analysis</topic><topic>Apoptosis</topic><topic>Arrays</topic><topic>Aspartate Aminotransferases - blood</topic><topic>Aspartate transaminase</topic><topic>Bioinformatics</topic><topic>Biology</topic><topic>Biopsy</topic><topic>Care and treatment</topic><topic>Cell cycle</topic><topic>Complications and side effects</topic><topic>Computation</topic><topic>Computer applications</topic><topic>Data analysis</topic><topic>Data processing</topic><topic>Death</topic><topic>Diagnostic systems</topic><topic>Gene expression</topic><topic>Genomics</topic><topic>Heart diseases</topic><topic>Humans</topic><topic>Hypoglycemia</topic><topic>Hypoxia</topic><topic>Influence</topic><topic>Ischemia</topic><topic>Liver</topic><topic>Liver - metabolism</topic><topic>Liver Transplantation - methods</topic><topic>Liver transplants</topic><topic>Metabolism</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>Organs</topic><topic>Perfusion</topic><topic>Predictions</topic><topic>Protein turnover</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Rodents</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>Studies</topic><topic>Tissue and Organ Procurement - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khorsandi, Shirin Elizabeth</au><au>Quaglia, Alberto</au><au>Salehi, Siamak</au><au>Jassem, Wayel</au><au>Vilca-Melendez, Hector</au><au>Prachalias, Andreas</au><au>Srinivasan, Parthi</au><au>Heaton, Nigel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The microRNA Expression Profile in Donation after Cardiac Death (DCD) Livers and Its Ability to Identify Primary Non Function</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-15</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0127073</spage><epage>e0127073</epage><pages>e0127073-e0127073</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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.</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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