Elevated urinary levels of urokinase-type plasminogen activator receptor (uPAR) in pancreatic ductal adenocarcinoma identify a clinically high-risk group

Abstract

BackgroundThe 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.MethodsThe 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.ResultsUrinary 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).ConclusionsA high urinary suPAR/creatinine ratio represents a useful marker for the identification of a subset of patients with poorer outcome.

suPAR and FSGS

“…Glomerular filtration is likely, given the molecular weight of suPAR. Yet, whereas serum suPAR correlates with the estimated glomerular filtration rate and urinary suPAR correlates with serum suPAR (12,18,19), urinary suPAR was higher in patients on dialysis. Time-evolution analysis and evaluation of the predictive performance of pretransplantation and posttransplantation urinary suPAR for FSGS recurrence after transplantation still need to be performed.…”

Current status of biomarker and targeted nanoparticle development: The precision oncology approach for pancreatic cancer therapy

“…Its function involves tumor growth, invasion metastasis, and angiogenesis by activation of matrix metalloproteinases and degradation of extracellular matrix A high level of uPA, therefore, has been associated with a poor prognostic biomarker for cancer patients [30]. Cellular receptor of uPA (uPAR) is anchored on plasma membrane via a glycosylphosphatidylinositol (GPI) and controls uPA mediated plasminogen activation [31].…”

“…It is overexpressed in tumor cells, especially invasive tumor cells, and several stromal cell types in tumor microenvironment, including angiogenic tumor endothelial cells, active fibroblasts, and active macrophages [32]. In addition, the soluble form of uPAR (suPAR) in urine was also reported as a useful marker for the identification of a subset of patients with poorer outcome [30]. A marked pathological characteristic of pancreatic cancer is the presence of an extensive tumor stroma that consists of 50-85% of a tumor mass.…”

Imaging of human pancreatic cancer xenografts by single-photon emission computed tomography with 99mTc-Hynic-PEG-AE105

“…Pancreatic cancer has an extremely poor prognosis; the median survival time for all patients is 4-6 months, and the overall five-year survival rate is 7.2% (1). Emerging evidence suggests that the serine-protease urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are significant in pancreatic cancer invasion and metastasis (5)(6)(7). Overexpression of uPAR in pancreatic cancer has been determined to be a strong and independent predictor of short overall survival (6).…”

“…Emerging evidence suggests that the serine-protease urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are significant in pancreatic cancer invasion and metastasis (5)(6)(7). Overexpression of uPAR in pancreatic cancer has been determined to be a strong and independent predictor of short overall survival (6). uPAR is recognized as a novel marker of cancer invasion and metastasis, and is a promising candidate as a molecular target for cancer therapy (8,9).…”