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Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases

BACKGROUND: In colorectal cancer (CRC), the liver is the most common site of metastasis. Surgical resection represents the standard therapy for patients with colorectal liver metastases (CRLM). However, 5-year survival rates after resection do not exceed 50%, and despite existing preoperative strati...

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Autores principales: Loosen, Sven H., Tacke, Frank, Binnebosel, Marcel, Leyh, Catherine, Vucur, Mihael, Heitkamp, Florian, Schoening, Wenzel, Ulmer, Tom F., Alizai, Patrick H., Trautwein, Christian, Koch, Alexander, Longerich, Thomas, Roderburg, Christoph, Neumann, Ulf P., Luedde, Tom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007468/
https://www.ncbi.nlm.nih.gov/pubmed/29930748
http://dx.doi.org/10.18632/oncotarget.25471
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author Loosen, Sven H.
Tacke, Frank
Binnebosel, Marcel
Leyh, Catherine
Vucur, Mihael
Heitkamp, Florian
Schoening, Wenzel
Ulmer, Tom F.
Alizai, Patrick H.
Trautwein, Christian
Koch, Alexander
Longerich, Thomas
Roderburg, Christoph
Neumann, Ulf P.
Luedde, Tom
author_facet Loosen, Sven H.
Tacke, Frank
Binnebosel, Marcel
Leyh, Catherine
Vucur, Mihael
Heitkamp, Florian
Schoening, Wenzel
Ulmer, Tom F.
Alizai, Patrick H.
Trautwein, Christian
Koch, Alexander
Longerich, Thomas
Roderburg, Christoph
Neumann, Ulf P.
Luedde, Tom
author_sort Loosen, Sven H.
collection PubMed
description BACKGROUND: In colorectal cancer (CRC), the liver is the most common site of metastasis. Surgical resection represents the standard therapy for patients with colorectal liver metastases (CRLM). However, 5-year survival rates after resection do not exceed 50%, and despite existing preoperative stratification algorithms it is still debated which patients benefit most from surgical treatment. The soluble urokinase plasminogen activator receptor (suPAR) has recently evolved as a promising biomarker for distinct clinical conditions. Here, we examined a potential role of suPAR as a biomarker in patients undergoing resection of CRLM. RESULTS: Correlating with upregulated uPAR tissue expression in resected metastases, serum concentrations of suPAR were significantly elevated in CRLM patients compared to healthy controls. Importantly, patients with preoperative suPAR serum levels above the identified ideal cut-off value of 4.83 ng/ml showed a significantly reduced overall survival after resection of CRLM, both in right- and left-sided primary CRC. Moreover, multivariate Cox regression analysis revealed preoperative suPAR serum levels as a prognostic factor for mortality. Additionally, elevated preoperative suPAR but not creatinine levels were a predictor of acute kidney injury (AKI) after CRLM resection, correlating with a longer postoperative hospitalization. CONCLUSION: SuPAR represents a promising novel biomarker in CRLM patients that might help to guide preoperative treatment decisions regarding patients’ outcome and to identify patients particularly susceptible to AKI. METHODS: Expression levels of uPAR were analyzed in CRLM tissue using RT-PCR and immunohistochemistry. SuPAR serum levels were measured by ELISA in 104 CRC patients undergoing hepatic resection for CRLM and 50 healthy controls.
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spelling pubmed-60074682018-06-21 Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases Loosen, Sven H. Tacke, Frank Binnebosel, Marcel Leyh, Catherine Vucur, Mihael Heitkamp, Florian Schoening, Wenzel Ulmer, Tom F. Alizai, Patrick H. Trautwein, Christian Koch, Alexander Longerich, Thomas Roderburg, Christoph Neumann, Ulf P. Luedde, Tom Oncotarget Research Paper BACKGROUND: In colorectal cancer (CRC), the liver is the most common site of metastasis. Surgical resection represents the standard therapy for patients with colorectal liver metastases (CRLM). However, 5-year survival rates after resection do not exceed 50%, and despite existing preoperative stratification algorithms it is still debated which patients benefit most from surgical treatment. The soluble urokinase plasminogen activator receptor (suPAR) has recently evolved as a promising biomarker for distinct clinical conditions. Here, we examined a potential role of suPAR as a biomarker in patients undergoing resection of CRLM. RESULTS: Correlating with upregulated uPAR tissue expression in resected metastases, serum concentrations of suPAR were significantly elevated in CRLM patients compared to healthy controls. Importantly, patients with preoperative suPAR serum levels above the identified ideal cut-off value of 4.83 ng/ml showed a significantly reduced overall survival after resection of CRLM, both in right- and left-sided primary CRC. Moreover, multivariate Cox regression analysis revealed preoperative suPAR serum levels as a prognostic factor for mortality. Additionally, elevated preoperative suPAR but not creatinine levels were a predictor of acute kidney injury (AKI) after CRLM resection, correlating with a longer postoperative hospitalization. CONCLUSION: SuPAR represents a promising novel biomarker in CRLM patients that might help to guide preoperative treatment decisions regarding patients’ outcome and to identify patients particularly susceptible to AKI. METHODS: Expression levels of uPAR were analyzed in CRLM tissue using RT-PCR and immunohistochemistry. SuPAR serum levels were measured by ELISA in 104 CRC patients undergoing hepatic resection for CRLM and 50 healthy controls. Impact Journals LLC 2018-06-05 /pmc/articles/PMC6007468/ /pubmed/29930748 http://dx.doi.org/10.18632/oncotarget.25471 Text en Copyright: © 2018 Loosen et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Loosen, Sven H.
Tacke, Frank
Binnebosel, Marcel
Leyh, Catherine
Vucur, Mihael
Heitkamp, Florian
Schoening, Wenzel
Ulmer, Tom F.
Alizai, Patrick H.
Trautwein, Christian
Koch, Alexander
Longerich, Thomas
Roderburg, Christoph
Neumann, Ulf P.
Luedde, Tom
Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases
title Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases
title_full Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases
title_fullStr Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases
title_full_unstemmed Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases
title_short Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases
title_sort serum levels of soluble urokinase plasminogen activator receptor (supar) predict outcome after resection of colorectal liver metastases
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007468/
https://www.ncbi.nlm.nih.gov/pubmed/29930748
http://dx.doi.org/10.18632/oncotarget.25471
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