Expression Profiling of Human Donor Lungs to Understand Primary Graft Dysfunction After Lung Transplantation

Lung transplantation is the treatment of choice for end‐stage pulmonary diseases. A limited donor supply has resulted in 4000 patients on the waiting list. Currently, 10–20% of donor organs offered for transplantation are deemed suitable under the selection criteria, of which 15–25% fail due to prim...

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Veröffentlicht in:American journal of transplantation 2007-10, Vol.7 (10), p.2396-2405
Hauptverfasser: Ray, M., Dharmarajan, S., Freudenberg, J., Zhang, W., Patterson, G. A.
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container_end_page 2405
container_issue 10
container_start_page 2396
container_title American journal of transplantation
container_volume 7
creator Ray, M.
Dharmarajan, S.
Freudenberg, J.
Zhang, W.
Patterson, G. A.
description Lung transplantation is the treatment of choice for end‐stage pulmonary diseases. A limited donor supply has resulted in 4000 patients on the waiting list. Currently, 10–20% of donor organs offered for transplantation are deemed suitable under the selection criteria, of which 15–25% fail due to primary graft dysfunction (PGD). This has spawned efforts to re‐examine the current selection criteria as well as search for alternative donor lungs selection criteria. In this study, we attempt to further our understanding of PGD by observing the changes in gene expression across donor lungs that developed PGD versus those that did not. From our analysis, we have obtained differentially expressed transcripts that were involved in signaling, apoptosis and stress‐activated pathways. Results also indicate that metallothionein 3 was over expressed in lungs that didn't develop PGD. This is the first such attempt to perform expression profiling of actual human lungs used for transplantation, for the identification of a molecular signature for PGD. Analysis of gene expression differences between human donor lungs that develop primary graft dysfunction and those that do not identified genes and biological pathways that are highly correlated with primary graft dysfunction.
doi_str_mv 10.1111/j.1600-6143.2007.01918.x
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Results also indicate that metallothionein 3 was over expressed in lungs that didn't develop PGD. This is the first such attempt to perform expression profiling of actual human lungs used for transplantation, for the identification of a molecular signature for PGD. Analysis of gene expression differences between human donor lungs that develop primary graft dysfunction and those that do not identified genes and biological pathways that are highly correlated with primary graft dysfunction.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/j.1600-6143.2007.01918.x</identifier><identifier>PMID: 17845573</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Biological and medical sciences ; Cadaver ; Cause of Death ; Female ; Gene Expression ; Gene Expression Profiling ; Gene pathway analysis ; human donor lungs ; Humans ; lung transplantation ; Lung Transplantation - pathology ; Male ; Medical sciences ; microarray gene expression ; Oligonucleotide Array Sequence Analysis ; Postoperative Complications - pathology ; primary graft dysfunction ; Retrospective Studies ; RNA - genetics ; RNA - isolation &amp; purification ; Surgery (general aspects). 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A.</creatorcontrib><title>Expression Profiling of Human Donor Lungs to Understand Primary Graft Dysfunction After Lung Transplantation</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>Lung transplantation is the treatment of choice for end‐stage pulmonary diseases. A limited donor supply has resulted in 4000 patients on the waiting list. Currently, 10–20% of donor organs offered for transplantation are deemed suitable under the selection criteria, of which 15–25% fail due to primary graft dysfunction (PGD). This has spawned efforts to re‐examine the current selection criteria as well as search for alternative donor lungs selection criteria. In this study, we attempt to further our understanding of PGD by observing the changes in gene expression across donor lungs that developed PGD versus those that did not. From our analysis, we have obtained differentially expressed transcripts that were involved in signaling, apoptosis and stress‐activated pathways. Results also indicate that metallothionein 3 was over expressed in lungs that didn't develop PGD. This is the first such attempt to perform expression profiling of actual human lungs used for transplantation, for the identification of a molecular signature for PGD. Analysis of gene expression differences between human donor lungs that develop primary graft dysfunction and those that do not identified genes and biological pathways that are highly correlated with primary graft dysfunction.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Cadaver</subject><subject>Cause of Death</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene Expression Profiling</subject><subject>Gene pathway analysis</subject><subject>human donor lungs</subject><subject>Humans</subject><subject>lung transplantation</subject><subject>Lung Transplantation - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>microarray gene expression</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Postoperative Complications - pathology</subject><subject>primary graft dysfunction</subject><subject>Retrospective Studies</subject><subject>RNA - genetics</subject><subject>RNA - isolation &amp; purification</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Tissue Donors - statistics &amp; numerical data</subject><subject>Transcription, Genetic</subject><subject>Treatment Failure</subject><issn>1600-6135</issn><issn>1600-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1PwjAYgBujEUT_gulFb5tvu6_u4IEAgoZED3huateSkdFiu0X4926OwNVe-ibv8349CGECIWnf0yYkKUCQkjgKKUAWAskJC_cXaHhKXJ7iKBmgG-83ACSjjF6jAclYnCRZNETVbL9zyvvSGvzhrC6r0qyx1XjRbIXBU2usw8vGrD2uLf40hXK-FqZo4XIr3AHPndA1nh68boysuzZjXau-Bq-cMH5XCVOLLnWLrrSovLo7_iO0epmtJotg-T5_nYyXgUxIxIIklREDSlUsFYCOIc4yCSmN87TIlaRUF6wgKU0SJbIiYxErlMhjTZhIcwXRCD32bXfOfjfK13xbeqmqdg9lG89TRpM8Z3ELsh6UznrvlOa7_ipOgHei-YZ3Dnnnk3ei-Z9ovm9L748zmq-tKs6FR7Mt8HAEhJei0q0JWfozlwNj0J47Qs8991NW6vDvBfj4bdVF0S_L_5nV</recordid><startdate>200710</startdate><enddate>200710</enddate><creator>Ray, M.</creator><creator>Dharmarajan, S.</creator><creator>Freudenberg, J.</creator><creator>Zhang, W.</creator><creator>Patterson, G. 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Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Tissue Donors - statistics &amp; numerical data</topic><topic>Transcription, Genetic</topic><topic>Treatment Failure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ray, M.</creatorcontrib><creatorcontrib>Dharmarajan, S.</creatorcontrib><creatorcontrib>Freudenberg, J.</creatorcontrib><creatorcontrib>Zhang, W.</creatorcontrib><creatorcontrib>Patterson, G. 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source MEDLINE; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Adult
Biological and medical sciences
Cadaver
Cause of Death
Female
Gene Expression
Gene Expression Profiling
Gene pathway analysis
human donor lungs
Humans
lung transplantation
Lung Transplantation - pathology
Male
Medical sciences
microarray gene expression
Oligonucleotide Array Sequence Analysis
Postoperative Complications - pathology
primary graft dysfunction
Retrospective Studies
RNA - genetics
RNA - isolation & purification
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Tissue Donors - statistics & numerical data
Transcription, Genetic
Treatment Failure
title Expression Profiling of Human Donor Lungs to Understand Primary Graft Dysfunction After Lung Transplantation
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