Transcriptional analysis identifies potential novel biomarkers associated with successful ex-vivo perfusion of human donor lungs
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Updated: Jun 17, 2026
Functional Assessment of the Donor Heart During Ex Situ Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography
Published on: October 11, 2022
John Robert Ferdinand1, Morvern Isabel Morrison2, Anders Andreasson2
1Molecular Immunity Unit, University of Cambridge, Department of Medicine, Cambridge, UK.
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.
