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Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation

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 lea...

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Autores principales: Lee, Nikki P., Wu, Haiyang, Ng, Kevin T.P., Luo, Ruibang, Lam, Tak-Wah, Lo, Chung-Mau, Man, Kwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027418/
https://www.ncbi.nlm.nih.gov/pubmed/29642405
http://dx.doi.org/10.3390/biomedicines6020041
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author Lee, Nikki P.
Wu, Haiyang
Ng, Kevin T.P.
Luo, Ruibang
Lam, Tak-Wah
Lo, Chung-Mau
Man, Kwan
author_facet Lee, Nikki P.
Wu, Haiyang
Ng, Kevin T.P.
Luo, Ruibang
Lam, Tak-Wah
Lo, Chung-Mau
Man, Kwan
author_sort Lee, Nikki P.
collection PubMed
description 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.
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spelling pubmed-60274182018-07-13 Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation Lee, Nikki P. Wu, Haiyang Ng, Kevin T.P. Luo, Ruibang Lam, Tak-Wah Lo, Chung-Mau Man, Kwan Biomedicines Article 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. MDPI 2018-04-06 /pmc/articles/PMC6027418/ /pubmed/29642405 http://dx.doi.org/10.3390/biomedicines6020041 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Nikki P.
Wu, Haiyang
Ng, Kevin T.P.
Luo, Ruibang
Lam, Tak-Wah
Lo, Chung-Mau
Man, Kwan
Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation
title Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation
title_full Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation
title_fullStr Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation
title_full_unstemmed Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation
title_short Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation
title_sort transcriptome analysis of acute phase liver graft injury in liver transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027418/
https://www.ncbi.nlm.nih.gov/pubmed/29642405
http://dx.doi.org/10.3390/biomedicines6020041
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