Abstract
Background: Urokinase plasminogen activator (uPA) is a serine protease which transforms inactive plasminogen into active plasmin. UPA plays an important role in neoplasm progression, cell growth and metastases through degradation of proteins in basement membranes and extracellular matrix. The aim of the study was the analysis of serum uPA concentration in patients suffering from pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) in order to determine its possible diagnostic and prognostic value. Methods: A study group involved 90 patients: 40 patients with PDAC, 30 patients with CP and 20 healthy individuals. UPA serum concentration was evaluated with ELISA. Results: We observed the threefold increase of uPA serum concentration in patients with PDAC (3,23 ng/ml), twofold increase of uPA serum concentration in patients with CP (2,18 ng/ml) compared to the control group (1,01 ng/ ml) (PDAC vs CP p<0,01; PDAC vs control p<0,01; CP vs control p<0,01). We revealed significant positive correlation between uPA serum level and CA19-9 (r=0.305 p<0,05) in all analyzed groups. We also found the significant correlation between serum uPA concentration and the survival time. Higher uPA concentration was observed in patients with shorter survival time (r=-0,391; p<0,05). Significant differences were present between uPA levels lower and greater than 2 ng/ml and the patients survival time (p<0,05). Conclusions: The presented results confirm the negative prognostic role of high serum uPA concentration in pancreatic cancer patients. The significant positive correlation between uPA serum concentration and CA19-9 provides new insights into the potential role of uPA in pancreatic cancer diagnosis.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) accounts for 3 % of all malignant neoplasms diagnosed each year in the world and is the fourth most common cause of cancer related deaths [1]
First study on the role of Urokinase plasminogen activator (uPA) in pancreatic ductal adenocarcinoma (PDAC) was conducted by Takeuchi et al [42] and confirmed high immunoexpression of this protein in 78% of pancreatic adenocarcinoma surgical specimen which correlated with shorter survival
The increase of uPA concentration was observed in patients with PDAC, and chronic pancreatitis (CP) compared to the control group
Summary
Pancreatic ductal adenocarcinoma (PDAC) accounts for 3 % of all malignant neoplasms diagnosed each year in the world and is the fourth most common cause of cancer related deaths [1]. Active plasmin catalyzes degradation of proteins in basement membranes and extracellular matrix and facilitates cancer cell invasion into surrounding tissue [21,22,23,24,25,26,27,28,29,30]. First study on the role of uPA in PDAC was conducted by Takeuchi et al [42] and confirmed high immunoexpression of this protein in 78% of pancreatic adenocarcinoma surgical specimen which correlated with shorter survival. UPA plays an important role in neoplasm progression, cell growth and metastases through degradation of proteins in basement membranes and extracellular matrix. The aim of the study was the analysis of serum uPA concentration in patients suffering from pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) in order to determine its possible diagnostic and prognostic value
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