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Integrated analysis and validation of metabolism-related genes in lung transplantation-induced cold ischemia/reperfusion injury

bioinformatics
immunology
pathology
respiratory-medicine
translational-medicine

Abstract

Background: Primary graft dysfunction (PGD) usually occurs within 72 hours after lung transplantation and is primarily caused by ischemia-reperfusion injury (IRI). Patients who develop PGD after lung transplantation tend to have a poor prognosis.

Methods: In this study, we explored the different expression of metabolism-related genes in lung transplantation-induced IRI and identified its potential molecular mechanisms by bioinformatics analysis. Next, we used two machine learning algorithms and further screened for key genes in them. Outside dataset GSE145989 was used to validate the accuracy of the model established by MLGs. In addition, we observed the distribution and localization of MLGs in the single-cell dataset GSE220797 and analyzed the correlation between MLGs and immune cells by the CIBERSORT immune infiltration algorithm. Finally, we validated the 9 MLGs by rat orthotopic left lung transplantation model and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), and we found that seven of these MLGs were consistent with the results of the bioinformatics analysis.

Results: We identified a number of MLGs (PDE4B, CDA, HMOX1, EHHADH, AMD1, GUCY1A1, GUCY1B1, UGCG, and FPGT) that are closely associated with ischemia-reperfusion injury induced by lung transplantation.
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