Gene Expression Profile in Liver Transplantation and the Influence of Gene Dysregulation Occurring in Deceased Donor Grafts

Background: Brain dead patients are the main source of organs for transplants. Brain death causes changes in peripheral organs. We define modifications of gene expression in specific pathways occurring in donor livers and their influence on gene expression profile of livers after transplant. Methods: We compared gene expression profile of both deceased donor livers and transplanted livers to gene expression data of liver tissue, retrieved from Array Express database, used as control. All expression data were obtained by microarray analysis. Results: The expression of about 33,000 genes has been compared in liver samples from three groups: deceased donor livers, transplanted livers two hours after reperfusion, and control livers. We found that about 900 genes are dysregulated in deceased donor versus control livers. Up-regulated genes are mainly involved in apoptosis, immune response and inflammation. Down-regulated genes are mostly involved in metabolism and electron transport. We also re-evaluated a group of genes that in a previous study were found dysregulated in transplanted livers when compared to donor livers. Most of these genes, but not all, were dysregulated also when compared to control livers. Moreover 317 additional genes, dysregulated after liver transplant, were identified in this study; they were undetectable in the previous study because they had the same dysregulation both in donor and in transplanted livers. Conclusions: Understanding molecular mechanisms that in the donor compromise graft function is crucial in order to discriminate between basal graft damages and ischemia-reperfusion injuries and therefore to identify therapeutic targets aiming to improve liver transplantation performances.