Soluble urokinase plasminogen activator receptor (suPAR) represents a novel biomarker for patients undergoing resection of colorectal liver metastases

Question:

In colorectal cancer (CRC), the liver is the most common site of metastasis. Surgical resection represents the standard potentially curative 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 not fully understood which patients benefit most from surgery. 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 circulating suPAR as a biomarker in patients undergoing resection of CRLM.

Methods:

Expression levels of uPAR, the membrane-bound source of circulating suPAR, were analysed in tissue samples of CRLM using RT-PCR and IHC. SuPAR serum levels were measured by ELISA in 104 patients undergoing surgical resection of CRLM as well as 50 healthy controls. Results were correlated with clinical data.

Results:

In line with an upregulation of uPAR in the CRLM tissue, serum levels of suPAR were significantly elevated in patients with CRLM compared to healthy controls. Patients with preoperative suPAR serum levels above our defined ideal cut-off value of 4.83 ng/ml showed a strikingly reduced overall survival after resection of CRLM, which could be confirmed for right- and left-sided primary CRC. Importantly, none of these patients reached long-term survival compared to patients with preoperative suPAR serum concentrations below the cut-off value. Moreover, multivariate Cox-regression analysis revealed preoperative suPAR serum levels as an independent prognostic factor in this setting. Additionally, elevated preoperative suPAR but not creatinine levels were a predictor of acute kidney injury after CRLM resection, correlating with a longer postoperative hospitalization.

Conclusions:

Serum levels of suPAR represent a promising novel biomarker in patients with resectable CRLM that might help to guide preoperative treatment decisions with regards to patients” outcome and the identification of patients particularly susceptible to postoperative acute kidney injury.