Transcriptional analysis identifies potential novel biomarkers associated with successful ex-vivo perfusion of human donor lungs.
Authors
Morrison, Morvern Isabel
Andreasson, Anders
Charlton, Catriona
Chhatwal, Alisha Kaur
Scott, William Earl
Borthwick, Lee Anthony
Clatworthy, Menna Ruth
Fisher, Andrew J
Publication Date
2022-04Journal Title
Clin Transplant
ISSN
0902-0063
Publisher
Wiley
Language
en
Type
Article
This Version
AO
VoR
Metadata
Show full item recordCitation
Ferdinand, J. R., Morrison, M. I., Andreasson, A., Charlton, C., Chhatwal, A. K., Scott, W. E., Borthwick, L. A., et al. (2022). Transcriptional analysis identifies potential novel biomarkers associated with successful ex-vivo perfusion of human donor lungs.. Clin Transplant https://doi.org/10.1111/ctr.14570
Description
Funder: NIHR Blood and Transplant Unit
Funder: NIHR Newcastle Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100012295
Funder: NIHR Cambridge Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100018956
Abstract
BACKGROUND: Transplantation is an effective treatment for end-stage lung disease, but the donor organ shortage is a major problem. Ex-vivo lung perfusion (EVLP) of extended criteria organs enables functional assessment to facilitate clinical decision-making around utilization, but the molecular processes occurring during EVLP, and how they differ between more or less viable lungs, remain to be determined. METHODS: We used RNA sequencing of lung tissue to delineate changes in gene expression occurring in 10 donor lungs undergoing EVLP and compare lungs that were deemed non-transplantable (n = 4) to those deemed transplantable (n = 6) following perfusion. RESULTS: We found that lungs deemed unsuitable for transplantation had increased induction of innate immune pathways and lower expression of oxidative phosphorylation related genes. Furthermore, the expression of SCGB1A1, a gene encoding an anti-inflammatory secretoglobin CC10, and other club cell genes was significantly decreased in non-transplantable lungs, while CHIT-1 was increased. Using a larger validation cohort (n = 17), we confirmed that the ratio of CHIT1 and SCGB1A1 protein levels in lung perfusate have potential utility to distinguish transplantable from non-transplantable lungs (AUC .81). CONCLUSIONS: Together, our data identify novel biomarkers that may assist with pre-transplant lung assessment, as well as pathways that may be amenable to therapeutic intervention during EVLPAQ6.
Keywords
ORIGINAL ARTICLE, ORIGINAL ARTICLES, artificial organs, chemokine receptors, chemokines, clinical trial, support devices: lung
Sponsorship
Medical Research Council (MR/N024907/1)
Identifiers
ctr14570
External DOI: https://doi.org/10.1111/ctr.14570
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332988
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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