Prognostic value of urokinase plasminogen activator system in non‑small cell lung cancer: A systematic review and meta‑analysis

Abstract

Abstract. Current relevant research suggests there are significant differences between the expression of the urokinase plasminogen activator (uPA) system in cancer tissues and in normal tissues. However, the potential effectiveness of the uPA system as a prognostic biomarker of non-small cell lung cancer (NSCLC) remains unclear. In the present study, a systematic review and meta-analysis were performed to evaluate the relevance of the uPA system in the prognosis of patients with NSCLC. Using the PubMed, EMBASE, Web of Science and Cochrane Library databases, data from relevant academic journal articles were extracted and subjected to analysis. Associations between expression profiles pertaining to the uPA system and the overall survival (OS) of patients with NSCLC were analyzed. The study incorporated data from 11 independent journal articles and these reports included a total of 937 patients with NSCLC. The meta-analysis results revealed that increased expression of urokinase plasminogen activator (uPA) and PA inhibitor type 1 (PAI-1) exhibited no significant association with poor OS [hazard ratio (HR)-uPA=1.07 (0.87-1.31), P=0.53; HR-PAI-1=1.02 (0.63-1.65), P=0.94]. Similarly, reduced expression of PAI type 2 (PAI-2) did not significantly correlate with poor OS [HR-PAI-2=1.58 (0.64-3.90); P= 0.32]. Notably, however, a significant association was observed between increased expression levels of uPA receptor (uPAR) and poor OS for NSCLC (1.04-2.15); P=0.03]. Therefore, the expression of uPAR in the uPA system of patients with NSCLC could be used as a novel clinical biomarker to evaluate the prognosis of NSCLC. The utilization of this biomarker may provide a platform for the further development of targeted drugs for the treatment of NSCLC. IntroductionOver the past 50 years, the worldwide incidence of lung cancer has significantly increased. In developed countries and large cities, lung cancer has become the most common type of cancer among males. In many countries, the number of mortalities due to lung cancer has surpassed the combined numbers from prostate cancer, breast cancer and gastrointestinal tumors (1,2). The majority of patients with lung cancer are males over the age of 40; however, the number of female patients has also increased significantly in recent years. Typically, lung cancer is divided into two categories: Small cell lung cancer (SCLC) and non-SCLC (NSCLC). As SCLC is distinct from NSCLC with respect to its biological behavior, treatment, prognosis and other features, the present study focused on the associations between NSCLC prognosis and the uPA system. Although there has been considerable progress in the diagnosis and treatment of NSCLC in recent years, the majority of cases are diagnosed only at an advanced stage. Consequently, the 5-year survival rate for NSCLC is ~15% (3). The invasion and distant metastasis of NSCLC cells are the most important biological characteristics of malignant lung tumors; these phenomena result in the associated low survival rates of patients with NSCLC (4). Thu...

FOXM1 functions collaboratively with PLAU to promote gastric cancer progression

“…PLAU activates the MAPK, Jak-Stat signal pathway and focal adhesion kinase systems by its direct binding to the uPAR (Urokinase-plasminogen activator receptor) or indirectly by activation of plasmin which releases growth factors from ECM [36]. The status of PLAU is also the biomarker of prognostic and predictive factor in breast cancer and non-small cell lung cancer [37,38] and synthetic antibody against PLAU has been demonstrated the inhibition ability to the cancer progression [39]. Using chicken embryo system, researchers demonstrated that PLAU play an important role in the early process of tumor cell dissemination which is the initial deliberation of cancer cell from the primary sites [40].…”

HAI-2 as a novel inhibitor of plasmin represses lung cancer cell invasion and metastasis

“…The uPA and uPA receptor (uPAR) are expressed in lung adenocarcinoma cells (Supplementary Figure S11 and ref. 27 ). Moreover, two SERPIN-type inhibitors, PAI-1 and α-2-antiplasmin, have been well-studied and irreversibly inhibit uPA and plasmin activity, respectively.…”

“…25,26 The recent meta-analysis of clinical patients' archival specimens have also suggested that uPA/ uPAR are clinical biomarkers for NSCLC. 27 Epithelial-mesenchymal transition (EMT) is a programmed process for cell transformation from epithelial to mesenchymal phenotypes, making cell polarity lost and cell motility increased to 15 18 Low risk (high HAl-2)…”

“…Low risk (high HAl-2) (20) 22 (35) 14 (21) 24 (38) 12 (18) 23 (36) 13 (21) 34 (54) 2 (3) 17 (26) 10 (15) 7 (11) 2 (3) 17 (26) 19 (29) 1 (1.5) 18 (28) 17 (27) 11 (17) 20 (31) 8 (13) 25 (39) 3 (5) 22 (34) 6 (9) 28 (43) promote metastasis. 28 During EMT process, the loss of E-cadherin is often accompanied with the up-regulation of mesenchymal neuron cadherin (N-cadherin) or a cytoskeleton protein Vimentin.…”

Anti-Cancer Effects of Green Tea Polyphenols Against Prostate Cancer

“…The activation of uPA plays important roles in carcinogenesis and cancer cell invasion [121,122]. The expression of uPA has been reported to be positively associated with the prognosis and outcome of various types of cancer [123,124]. Therefore, we suggest that further studies need to be conducted to understand the pathological roles of uPA regulated by GTP.…”