Transcriptional analysis identifies potential novel biomarkers associated with successful ex-vivo perfusion of human donor lungs.
Morrison, Morvern Isabel
Chhatwal, Alisha Kaur
Scott, William Earl
Borthwick, Lee Anthony
Fisher, Andrew J
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Ferdinand, J., 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
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
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.
ORIGINAL ARTICLE, ORIGINAL ARTICLES, artificial organs, chemokine receptors, chemokines, clinical trial, support devices: lung
Medical Research Council (MR/N024907/1)
External DOI: https://doi.org/10.1111/ctr.14570
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332988