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Up‐regulated LRRN2 expression as a marker for graft quality in living donor liver transplantation

The quality and size of liver grafts are critical factors that influence living‐donor liver transplantation (LDLT) function and safety. However, the biomarkers used for predicting graft quality are lacking. In this study, we sought to identify unique graft quality markers, aside from donor age, by u...

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Autores principales: Tomiyama, Takahiro, Yamamoto, Takuya, Takahama, Shokichi, Toshima, Takeo, Itoh, Shinji, Harada, Noboru, Shimokawa, Mototsugu, Okuzaki, Daisuke, Mori, Masaki, Yoshizumi, Tomoharu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512467/
https://www.ncbi.nlm.nih.gov/pubmed/35894759
http://dx.doi.org/10.1002/hep4.2033
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author Tomiyama, Takahiro
Yamamoto, Takuya
Takahama, Shokichi
Toshima, Takeo
Itoh, Shinji
Harada, Noboru
Shimokawa, Mototsugu
Okuzaki, Daisuke
Mori, Masaki
Yoshizumi, Tomoharu
author_facet Tomiyama, Takahiro
Yamamoto, Takuya
Takahama, Shokichi
Toshima, Takeo
Itoh, Shinji
Harada, Noboru
Shimokawa, Mototsugu
Okuzaki, Daisuke
Mori, Masaki
Yoshizumi, Tomoharu
author_sort Tomiyama, Takahiro
collection PubMed
description The quality and size of liver grafts are critical factors that influence living‐donor liver transplantation (LDLT) function and safety. However, the biomarkers used for predicting graft quality are lacking. In this study, we sought to identify unique graft quality markers, aside from donor age, by using the livers of non‐human primates. Hepatic gene microarray expression data from young and elderly cynomolgus macaques revealed a total of 271 genes with significantly increased expression in the elderly. These candidate genes were then narrowed down to six through bioinformatics analyses. The expression patterns of these candidate genes in human donor liver tissues were subsequently examined. Importantly, we found that grafts exhibiting up‐regulated expression of these six candidate genes were associated with an increased incidence of liver graft failure. Multivariable analysis further revealed that up‐regulated expression of LRRN2 (encoding leucine‐rich repeat protein, neuronal 2) in donor liver tissue served as an independent risk factor for graft failure (odds ratio 4.50, confidence interval 2.08–9.72). Stratification based on graft expression of LRRN2 and donor age was also significantly associated with 6‐month graft survival rates. Conclusion: Up‐regulated LRRN2 expression of liver graft is significantly correlated with graft failure in LDLT. In addition, combination of graft LRRN2 expression and donor age may represent a promising marker for predicting LDLT graft quality.
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spelling pubmed-95124672022-09-30 Up‐regulated LRRN2 expression as a marker for graft quality in living donor liver transplantation Tomiyama, Takahiro Yamamoto, Takuya Takahama, Shokichi Toshima, Takeo Itoh, Shinji Harada, Noboru Shimokawa, Mototsugu Okuzaki, Daisuke Mori, Masaki Yoshizumi, Tomoharu Hepatol Commun Original Articles The quality and size of liver grafts are critical factors that influence living‐donor liver transplantation (LDLT) function and safety. However, the biomarkers used for predicting graft quality are lacking. In this study, we sought to identify unique graft quality markers, aside from donor age, by using the livers of non‐human primates. Hepatic gene microarray expression data from young and elderly cynomolgus macaques revealed a total of 271 genes with significantly increased expression in the elderly. These candidate genes were then narrowed down to six through bioinformatics analyses. The expression patterns of these candidate genes in human donor liver tissues were subsequently examined. Importantly, we found that grafts exhibiting up‐regulated expression of these six candidate genes were associated with an increased incidence of liver graft failure. Multivariable analysis further revealed that up‐regulated expression of LRRN2 (encoding leucine‐rich repeat protein, neuronal 2) in donor liver tissue served as an independent risk factor for graft failure (odds ratio 4.50, confidence interval 2.08–9.72). Stratification based on graft expression of LRRN2 and donor age was also significantly associated with 6‐month graft survival rates. Conclusion: Up‐regulated LRRN2 expression of liver graft is significantly correlated with graft failure in LDLT. In addition, combination of graft LRRN2 expression and donor age may represent a promising marker for predicting LDLT graft quality. John Wiley and Sons Inc. 2022-07-27 /pmc/articles/PMC9512467/ /pubmed/35894759 http://dx.doi.org/10.1002/hep4.2033 Text en © 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Tomiyama, Takahiro
Yamamoto, Takuya
Takahama, Shokichi
Toshima, Takeo
Itoh, Shinji
Harada, Noboru
Shimokawa, Mototsugu
Okuzaki, Daisuke
Mori, Masaki
Yoshizumi, Tomoharu
Up‐regulated LRRN2 expression as a marker for graft quality in living donor liver transplantation
title Up‐regulated LRRN2 expression as a marker for graft quality in living donor liver transplantation
title_full Up‐regulated LRRN2 expression as a marker for graft quality in living donor liver transplantation
title_fullStr Up‐regulated LRRN2 expression as a marker for graft quality in living donor liver transplantation
title_full_unstemmed Up‐regulated LRRN2 expression as a marker for graft quality in living donor liver transplantation
title_short Up‐regulated LRRN2 expression as a marker for graft quality in living donor liver transplantation
title_sort up‐regulated lrrn2 expression as a marker for graft quality in living donor liver transplantation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512467/
https://www.ncbi.nlm.nih.gov/pubmed/35894759
http://dx.doi.org/10.1002/hep4.2033
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