Rw. Stephens et al., Plasma urokinase receptor levels in patients with colorectal cancer: Relationship to prognosis, J NAT CANC, 91(10), 1999, pp. 869-874
Background: The proteolytic enzyme plasmin, which is generated from the pre
cursor plasminogen by the action of urokinase plasminogen activator, is tho
ught to play a role in tumor cell invasion and metastasis. Urokinase plasmi
nogen activator receptor (uPAR) is functionally involved in the cell surfac
e activation (i.e., cleavage) of plasminogen. Increased tumor tissue levels
of uPAR are associated with poor prognosis in several types of cancer. Thi
s retrospective study was undertaken to test the relationship between preop
erative plasma levels of soluble uPAR (suPAR) and survival in patients with
colorectal cancer. Methods: suPAR levels in preoperative plasma from 591 p
atients with colorectal cancer were determined by use of a kinetic enzyme-l
inked immunosorbent assay and analyzed with respect to associations with po
stoperative survival, Dukes' stage, age, and serum carcinoembryonic antigen
level. Plasma suPAR measurements were log transformed for survival analysi
s, which employed the Kaplan-Meier method and the Cox proportional hazards
model. All P values reported are two-sided. Results: Univariate analysis, u
sing 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), divide
d patients with Dukes' stage B, C, or D disease into statistically differen
t prognostic groups. In multivariate Cox analysis including Dukes' stage, a
ge, and carcinoembryonic antigen level, the suPAR concentration independent
ly 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 eval
uate the utility of plasma suPAR measurements and cut points in identifying
high-risk patients among those with early stage disease.