4247 Background: Urokinase-type plasminogen activator (uPA) is a serine protease associated with tumor cell migration, angiogenesis, metastasis, and invasion. uPA has been reported to be secreted by tumors, adjacent stromal cells, and fibroblasts, and has been proposed as a prognostic factor in breast, liver, and colon cancers.
METHODS
This study determined serum uPA levels in a phase III clinical trial of 149 patients with advanced pancreatic cancer. A double-antibody sandwich ELISA (Oncogene Science Diagnostics, Cambridge, MA) was employed to determine the pretreatment serum uPA levels in 149 pancreatic cancer patients enrolled in a randomized, double-blind, placebo-controlled phase III trial. A healthy control group consisting of 47 males and 62 females was used to determine control serum levels of uPA.
RESULTS
The results showed that serum uPA levels were significantly higher in female (1.37 ng/mL) compared to male (1.15 ng/mL) healthy control individuals (p = 0.0002). Within the female control group, there was no significant difference in serum uPA levels between premenopausal (1.39 ng/mL, n = 47) and post-menopausal (1.31 ng/mL, n = 15) females (p = 0.39). Cutpoint analysis was performed separately using the mean + 2 SD for female (1.94 ng/mL) and male (1.74 ng/mL) controls. In the pancreatic cancer patients, serum uPA levels were elevated in 23 of 63 (36%) female patients, and 40 of 86 (46%) male patients. In addition, mean serum uPA levels were significantly higher in both female (1.85 ng/mL, p<0.00001) and male (1.96 ng/mL, p<0.00001) pancreatic cancer patients when compared to controls. Patients with elevated serum uPA trended toward a shortened survival (median 127 days) compared to patients with normal serum uPA levels (median 198 days)(p = 0.083).
CONCLUSIONS
Serum uPA levels are significantly elevated in a proportion of advanced pancreatic cancer patients, and these patients trend toward shortened survival. Serum uPA levels may have potential for selection of patients to be treated with novel uPA small-molecule inhibitors. [Table: see text].