Elevated urinary levels of urokinase-type plasminogen activator receptor (uPAR) in pancreatic ductal adenocarcinoma identify a clinically high-risk group
- Equal contributors
1 Department of Pathology and Diagnostics, University of Verona, Verona, Italy
2 ARC-Net Research Center, University of Verona, Policlinico G.B. Rossi, Verona, Italy
3 BoNetwork, San Raffaele Scientific Institute, Milan, Italy
4 Department of Molecular Biology and Functional Genomics, San Raffaele Scientific Institute, Milan, Italy
5 Department of Surgery, University of Verona, Verona, Italy
6 Laboratory of chemical, clinical and haematological analyses, Hospitals of Verona, Verona, Italy
BMC Cancer 2011, 11:448 doi:10.1186/1471-2407-11-448Published: 14 October 2011
The urokinase plasminogen activator receptor is highly expressed and its gene is amplified in about 50% of pancreatic ductal adenocarcinomas; this last feature is associated with worse prognosis. It is unknown whether the level of its soluble form (suPAR) in urine may be a diagnostic-prognostic marker in these patients.
The urinary level of suPAR was measured in 146 patients, 94 pancreatic ductal adenocarcinoma and 52 chronic pancreatitis. Urine from 104 healthy subjects with similar age and gender distribution served as controls. suPAR levels were normalized with creatinine levels (suPAR/creatinine, ng/mg) to remove urine dilution effect.
Urinary suPAR/creatinine values of pancreatic ductal adenocarcinoma patients were significantly higher (median 9.8; 25th-75th percentiles 5.3-20.7) than those of either healthy donors (median 0; 0-0.5) or chronic pancreatitis patients (median 2.7; 0.9-4.7). The distribution of values among cancer patients was widespread and asymmetric, 53% subjects having values beyond the 95th percentile of healthy donors. The values of suPAR/creatinine did not correlate with tumour stage, Ca19-9 or CEA levels. Higher values correlated with poor prognosis among non-resected patients at univariate analysis; multivariate Cox regression identified high urinary suPAR/creatinine as an independent predictor of poor survival among all cancer patients (odds ratio 2.10, p = 0.0023), together with tumour stage (stage III odds ratio 2.65, p = 0.0017; stage IV odds ratio 4.61, p < 0.0001) and female gender (odds ratio 1.85, p = 0.01).
A high urinary suPAR/creatinine ratio represents a useful marker for the identification of a subset of patients with poorer outcome.