Prognostic value of intact and cleaved forms of the urokinase plasminogen activator receptor in a retrospective study of 518 colorectal cancer patients

Abstract

Background. The levels of the soluble urokinase plasminogen activator receptor (suPAR) in blood have been shown to correlate with prognosis in various cancers. Plasma levels of the combined suPAR forms have previously shown to be a strong prognostic marker in the present cohort of CRC patients and could potentially identify high-risk patients among those with early stage disease. In order to investigate whether the individual suPAR forms are stronger prognostic markers than the combined amount we measured the different uPAR forms in serum from the same cohort and evaluated their prognostic significance. Material and methods. The different suPAR forms were measured in serum preoperatively collected from 518 patients. Patients were followed up to nine years (median 7.9 years) and the primary endpoint was overall survival. The different suPAR forms were measured using Time Resolved Fluorescence Immunoassays(TR-FIAs): Intact, suPAR(I–III) by TR-FIA 1; intact and cleaved, suPAR(I–III)+(II–III) by TR-FIA 2; and liberated uPAR(I) by TR-FIA 3. Results. All three uPAR variants demonstrated prognostic significance when evaluated individually. In a multivariable analysis suPAR(I–III)+(II–III) and the liberated uPAR(I) were shown to be independent markers of prognosis (HR=1.74, CI:1.33–2.26; p <0.0001 and HR=1.32; CI:1.02–1.71; p=0.036 respectively), and independent of the clinical baseline variables: age, gender, tumor stage and localization. Conclusion. This study demonstrated that suPAR(I–III)+(II–III) and the liberated uPAR(I) in serum are independent prognostic markers in CRC.