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.
Highlights
RESULTSColorectal cancer (CRC) represents the third most common type of cancer worldwide and has remained one of the leading causes of cancer-related death to date [1]
SuPAR serum levels were measured by enzyme-linked immunosorbent assay (ELISA) in 104 colorectal cancer (CRC) patients undergoing hepatic resection for colorectal liver metastases (CRLM) and 50 healthy controls
For resectable CRLM patients, surgical removal of the liver metastases has evolved as the standard curative therapeutic approach [4]
Summary
RESULTSColorectal cancer (CRC) represents the third most common type of cancer worldwide and has remained one of the leading causes of cancer-related death to date [1]. The lifetime incidence of colorectal liver metastases (CRLM) in CRC patients is approximately 50% [3]. The overall 5-year survival rate after surgical resection varies between 25 and 58% [6] compared to less than 1% for patients with advanced stage disease undergoing systemic chemotherapy [5], corroborating the medical benefit of a surgical treatment. Despite the existence of prognostic algorithms such as the FONGscore [9] and other preoperative assessment strategies (including laboratory parameters, imaging techniques and the clinical performance status), it is still not fully understood which patients benefit from surgical resection of CRLM in terms of overall survival (OS). Surgical resection represents the standard therapy for patients with colorectal liver metastases (CRLM). 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. We examined a potential role of suPAR as a biomarker in patients undergoing resection of CRLM
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