Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases
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Sven H. Loosen1,*, Frank Tacke1,*, Marcel Binnebosel2, Catherine Leyh3, Mihael Vucur3, Florian Heitkamp3, Wenzel Schoening2, Tom F. Ulmer2, Patrick H. Alizai2, Christian Trautwein1, Alexander Koch1, Thomas Longerich4,5, Christoph Roderburg1,#, Ulf P. Neumann2,6,# and Tom Luedde1,3,#
1Department of Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany
2Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074 Aachen, Germany
3Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, 52074 Aachen, Germany
4Institute of Pathology, University Hospital RWTH Aachen, 52074 Aachen, Germany
5Division of Translational Gastrointestinal Pathology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany
6Department of Surgery, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands
*These authors share first authorship
#These authors share senior authorship
Tom Luedde, email: [email protected]
Keywords: cancer; biomarker; acute kidney injury; prognosis; CEA
Received: April 19, 2018 Accepted: May 08, 2018 Published: June 05, 2018
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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