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

// Sven H. Loosen 1, * , Frank Tacke 1, * , Marcel Binnebosel 2 , Catherine Leyh 3 , Mihael Vucur 3 , Florian Heitkamp 3 , Wenzel Schoening 2 , Tom F. Ulmer 2 , Patrick H. Alizai 2 , Christian Trautwein 1 , Alexander Koch 1 , Thomas Longerich 4, 5 , Christoph Roderburg 1, # , Ulf P. Neumann 2, 6, # and Tom Luedde 1, 3, # 1 Department of Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany 2 Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074 Aachen, Germany 3 Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, 52074 Aachen, Germany 4 Institute of Pathology, University Hospital RWTH Aachen, 52074 Aachen, Germany 5 Division of Translational Gastrointestinal Pathology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany 6 Department of Surgery, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands * These authors share first authorship # These authors share senior authorship Correspondence to: Tom Luedde, email: tluedde@ukaachen.de Keywords: cancer; biomarker; acute kidney injury; prognosis; CEA Received: April 19, 2018      Accepted: May 08, 2018      Published: June 05, 2018 ABSTRACT 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.