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Gene expression profile in human orthotopic liver transplantation

ABSTRACT: We have studied the genes activated in human liver transplantation to identify potential target genes for the prevention or treatment of related injuries. In a first protocol, in order to evaluate the effect of Ischemia-Reperfusion Injury (IRI) on gene expression profile, we compared gene expression levels in transplanted-reperfused livers versus basal values in donor livers, identifying 795 genes significantly modified in human liver after transplantation. Some genes are likely to be completely activated by IRI, as they are not expressed at all in basal livers. In a second protocol, in order to identify gene dysregulations already present in donor livers, which might affect gene expression profile after transplantation, gene expression evaluated in the first study was compared to control livers (espression data retrieved from ArrayExpress database). About 900 genes in donor livers are dysregulated if compared to the control condition. At least 400 of them remain dysregulated or become more and more dysregulated after transplantation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE14951 | GEO | 2009/10/01

SECONDARY ACCESSION(S): PRJNA111815

REPOSITORIES: GEO

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Project description:INTRODUCTION Ischemia and reperfusion injury (IRI)-elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest 1. Ischemia-reperfusion injury is also a major challenge during organ transplantation and cardiothoracic, vascular and general surgery 1. IRI, one of the biggest challenges for organ transplantation, continues to be a vital source of morbidity among recipients, especially in liver transplantation 2. With the enlarging shortage of available donor livers, the increased use of extended criteria donor grafts further increases IRI, adversely affecting both short-term and long-term outcomes of graft and patient survival 3. Numerous studies have investigated the benefits of pharmacological, heat shock, and ischemic preconditioning interventions aimed at decreasing liver IRI 4. However, the benefit was limited. Our center has been making great effort in conquering IRI and have developed a novel surgical technique called ischemia-free liver transplantation 5. It is an ultimate method to overcome IRI in liver transplantation, but there is still a long way to popularize it. As a result, it is still of great significance to study IRI and identify the core genes in the process and the underlying mechanism. Comprehensive bioinformatics analysis has been increasingly important as a method to study various pathological and physiological condition 6. By enrolling multiple omics or combining different types of omics, comprehensive bioinformatics analysis was able to recognize key factors that could have potentially pathogenic impact such as gene expression, protein function, and downstream pathways. With the rapid development of high-throughput sequencing technologies, several transcriptomic datasets on IRI of liver transplantation have become available in the Gene Expression Omnibus (GEO) database. Herein, we recruited 3 GEO datasets to conduct comprehensive analysis with the GEO dataset from our center. Moreover, we performed the first proteome of liver tissues to study liver IRI. Then the transcriptome and proteome were used for combined analysis to reveal key factors in liver IRI.

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Gene expression profile in human orthotopic liver transplantation

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