Dataset Information

Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation.

ABSTRACT:

Background

Liver transplantation remains the treatment of choice for a selected group of hepatocellular carcinoma (HCC) patients. However, the long-term benefit is greatly hampered by post-transplant HCC recurrence. Our previous studies have identified liver graft injury as an acute phase event leading to post-transplant tumor recurrence.

Methods

To re-examine this acute phase event at the molecular level and in an unbiased way, RNA sequencing (RNA-Seq) was performed on liver graft biopsies obtained from the transplant recipients two hours after portal vein reperfusion with an aim to capture frequently altered pathways that account for post-transplant tumor recurrence. Liver grafts from recurrent recipients (n = 6) were sequenced and compared with those from recipients without recurrence (n = 5).

Results

RNA expression profiles comparison pointed to several frequently altered pathways, among which pathways related to cell adhesion molecules were the most involved. Subsequent validation using quantitative polymerase chain reaction confirmed the differential involvement of two cell adhesion molecules HFE (hemochromatosis) and CD274 and their related molecules in the acute phase event.

Conclusion

This whole transcriptome strategy unravels the molecular landscape of liver graft gene expression alterations, which can identify key pathways and genes that are involved in acute phase liver graft injury that may lead to post-transplant tumor recurrence.

SUBMITTER: Lee NP

PROVIDER: S-EPMC6027418 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Publications

Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation.

Lee Nikki P NP Wu Haiyang H Ng Kevin T P KTP Luo Ruibang R Lam Tak-Wah TW Lo Chung-Mau CM Man Kwan K

Biomedicines 20180406 2

<h4>Background</h4>Liver transplantation remains the treatment of choice for a selected group of hepatocellular carcinoma (HCC) patients. However, the long-term benefit is greatly hampered by post-transplant HCC recurrence. Our previous studies have identified liver graft injury as an acute phase event leading to post-transplant tumor recurrence.<h4>Methods</h4>To re-examine this acute phase event at the molecular level and in an unbiased way, RNA sequencing (RNA-Seq) was performed on liver graf ...[more]

PMID: 29642405

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Project description:Background: As an “immune-privileged organ”, the rate of spontaneous and operational tolerance was higher after liver transplantation (LT) compared with other solid organs. However, modern immunosuppression regimens still have multiple complications, which require a deeper understanding of the real mechanism of inducing immune tolerance. Methods: Homogenic and allogeneic rat LT models were established, and recipient tissue was collected on postoperative day 7. The degree of LT rejection was evaluated by liver pathological changes and liver function. Differentially expressed genes (DEGs) were detected by transcriptome sequencing and identified by RT-PCR. The functional properties of DEGs were characterized by the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway analyses. The cells infiltrating the graft and recipient spleen and peripheral blood were evaluated by immunofluorescence assays and flow cytometry. Result: A total of 1465 DEGs were screened, including 1177 up-regulated genes and 288 down-regulated genes. GO enrichment and KEGG pathway analysis indicated that DEGs were involved in several immunobiological processes, including immune system process, immune response, regulation of immune response, T cell activation, cytokine-cytokine receptor interaction, allograft rejection, Th1,Th2 and Th17 cell differentiation. Reactome results showed that PD-1 signaling was also enriched. Further research confirmed that the expression of multiple immune cell markers increased, and most marker of T cell exhaustion changed significantly. Flow cytometry results showed that the proportion of Treg decreased in the allogeneic group, while CD4+PD-1+ T and CD8+PD-1+ T cells increased. Conclusion: This study, to our knowledge, was the first to reveal the impact of liver transplantation rejection on the liver at the omics level. Our results revealed that the progression of LT rejection involves multiple immune cells, activation of various immune pathways and special changes of immune checkpoints, which provides potential reference for potential risk assessment and pathogenesis. However, further clinical validation is also needed.

Dataset Information

Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation.

Background

Methods

Results

Conclusion

Publications

Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation.

Similar Datasets

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