The concentration of the cleaved suPAR forms in pre- and postoperative plasma samples improves the prediction of survival in colorectal cancer: A nationwide multicenter validation and discovery study

摘要

Background and Objectives The aim was to evaluate the prognostic biomarker potential of the soluble urokinase-type plasminogen activator receptor (suPAR) in plasma samples collected pre- and postoperatively from patients resected for colorectal cancer (CRC). Methods Patients with CRC were recruited prospectively at six centers from 2006 to 2008. Preoperative plasma samples were available from 494 patients and from 328 of these patients at 6 months postoperatively. Determinations of intact soluble uPAR (suPAR) suPAR(I-III) and the cleaved forms suPAR(I-III) + (II-III) and uPAR(I) were performed. Clinical data were retrieved retrospectively. Results In a multivariable model based on preoperative plasma samples suPAR(I-III) + (II-III) and uPAR(I) showed an independent statistically significant association to long term survival. When including the change in biomarker level between the pre- and postoperatively samples the hazard ratios were 3.06 (95% confidence interval [CI], 1.78-5.28; P < .0001) and 2.24 (95% CI, 1.59-3.16; P < .0001) for suPAR(I-III) + (II-III) and uPAR(I), respectively. A one-unit decrease in biomarker levels between the pre- and postoperative levels resulted in a 55% and 34% reduction in the risk estimate of death for suPAR(I-III) + (II-III) and uPAR(I), respectively. Conclusion This study validates previously findings regarding the prognostic significance of suPAR in preoperative samples. The inclusion of postoperative samples added further prognostic information.