Plasma Urokinase Receptor Levels in Patients With Colorectal Cancer: Relationship to Prognosis

Abstract

BACKGROUND: The proteolytic enzyme plasmin, which is generated from the precursor plasminogen by the action of urokinase plasminogen activator, is thought to play a role in tumor cell invasion and metastasis. Urokinase plasminogen activator receptor (uPAR) is functionally involved in the cell surface activation (i.e., cleavage) of plasminogen. Increased tumor tissue levels of uPAR are associated with poor prognosis in several types of cancer. This retrospective study was undertaken to test the relationship between preoperative plasma levels of soluble uPAR (suPAR) and survival in patients with colorectal cancer. METHODS: suPAR levels in preoperative plasma from 591 patients with colorectal cancer were determined by use of a kinetic enzyme-linked immunosorbent assay and analyzed with respect to associations with postoperative survival, Dukes' stage, age, and serum carcinoembryonic antigen level. Plasma suPAR measurements were log transformed for survival analysis, which employed the Kaplan-Meier method and the Cox proportional hazards model. All P values reported are two-sided. RESULTS: Univariate analysis, using the log-transformed suPAR concentrations, demonstrated that there was an increasing risk of mortality with increasing plasma suPAR level (P<.0001). An arbitrary cut point, the median for all patients (1.37 ng/mL), divided patients with Dukes' stage B, C, or D disease into statistically different prognostic groups. In multivariate Cox analysis including Dukes' stage, age, and carcinoembryonic antigen level, the suPAR concentration independently predicted survival (P<.0001). CONCLUSIONS: The preoperative plasma suPAR level independently predicted survival of patients with colorectal cancer. Further studies of plasma suPAR in patients with cancer are needed to evaluate the utility of plasma suPAR measurements and cut points in identifying high-risk patients among those with early stage disease.