Transcriptional signatures in donor lungs from donation after cardiac death vs after brain death: A functional pathway analysis

BACKGROUND: Lung donation after cardiac death (DCD), in contrast to donation after brain death (DBD), is a promising and increasingly common method to help relieve the shortage of donor organs. We aimed to study the differential gene expression profiles in lungs of DCD and DBD patients and interpreted the differences using functional pathway analysis. METHODS: We performed microarray studies on pre- and post-transplant lung tissues from 7 DCD and 12 matched DBD patients. Gene profiling was performed by Affymetrix human gene U-133 plus 2 GeneChip on 35 lung tissues. Principal Component Analysis (PCA), Significance Analysis of Microarray (SAM) and Hierarchical Clustering were performed to identify gross gene expression features and the lists of significantly regulated genes. We used Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) to determine functional significance and the genomic network relationship. RESULTS: Gene expression profiles between DCD and DBD demonstrated a clear distinction by PCA, especially in the pre-transplant period. The gene sets enriched in DBD mapped to innate immunity, intracellular signaling, cytokine interaction, cell communication and apoptosis pathways. The networks produced by IPA showed that pro-inflammatory nodes played major role in pre-transplant DBD networks. However, the number of differentially regulated transcripts or gene sets decreased markedly after transplantation between DBD and DCD. CONCLUSION: Analysis of gene expression profiles in donor lungs showed significant differences in pathway activation between DBD and DCD lungs. The observation of fewer inflammatory features of DCD donor lungs suggests safe application of lung transplantation in properly preserved DCD donor lungs. J Heart Lung Transplant 2011;30:289-98 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.