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

Abstract

BackgroundIn 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.ResultsCorrelating 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.ConclusionSuPAR 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.MethodsExpression 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.

Soluble Urokinase Plasminogen Activator Receptor (suPAR) Concentrations Are Elevated in Patients with Neuroendocrine Malignancies

“…Our data are in line with previous publications showing elevated suPAR serum levels in manifold cancers. Just recently, we demonstrated that concentrations of suPAR are elevated in patients with cholangiocellular carcinoma (CCA) [18] as well as in patients with pancreatic ductal adenocarcinoma (PDAC) [34] or colorectal cancer (CRC) [20]. Notably, serum concentrations of suPAR in our cohort of patients with NET are numerically very similar to those found in CCA, PDAC and CRC.…”

“…suPAR was identified as a biomarker in patients with inflammatory and infectious diseases [ 13 , 14 , 15 , 16 ]. Moreover, a prognostic role for suPAR serum levels has been demonstrated in different cancers including pancreatic, cholangiocellular and colorectal malignancies [ 17 , 18 , 19 , 20 ]. However, in NET no data on a potential role of circulating suPAR as a biomarker for prediction of patients’ prognosis or response to therapies have been reported so far.…”

Circulating levels of soluble urokinase plasminogen activator receptor predict outcome after resection of biliary tract cancer

“…12 SuPAR might also be an interesting circulating biomarker as recently shown for patients with sepsis 13 and cancer. [14][15][16] In BTC, preliminary data described a correlation between high tumoral uPAR expression and tumor invasion and metastasis. 17,18 However, there is insufficient data on a potential role of circulating suPAR as a biomarker in patients with BTC.…”

Soluble Urokinase Receptor and Liver Disease

“…In liver malignancies, induction of uPAR was observed in colorectal liver metastases, whereas normal liver tissues showed very weak uPAR staining. However, serum suPAR levels increased after surgical resection of the tumor, suggesting that liver metastases are not a major source of circulating suPAR …”

“…They found that patients with suPAR levels >9.5 ng/mL at the beginning of the study progressed earlier to HCC; thus, they suggested that serum suPAR serves as a potential screening tool for the early diagnosis of HCC in patients with chronic liver disorders . In terms of liver metastases, Loosen et al measured suPAR levels in 104 patients undergoing hepatic resection for colorectal liver metastases. They found that the preoperative, but not postoperative, suPAR level was a prognostic factor for mortality.…”