Serum Levels of Angiogenic Factors and their Prognostic Relevance in Bladder Cancer

Abstract

Angiogenesis plays a critical role in tumor growth. VEGF, angiopoietins (Ang-1, Ang-2) and their tyrosine kinase receptor Tie2 are major regulators of angiogenesis. The aim of this study was to evaluate the prognostic value of the serum levels of these factors in bladder cancer. We analyzed the serum samples of 117 bladder cancer patients and 64 healthy volunteers by enzyme linked immunosorbent assay (ELISA) for Ang-1, Ang-2, VEGF and the extracellular domain of Tie2. The statistical evaluation of the obtained data was performed via Kaplan-Meier log-rank test, univariate Cox analyses as well as Cox proportional hazards regression model. Serum Ang-1 levels of bladder cancer patients were significantly higher (p < 0.001), while soluble Ang-2 and Tie2 levels were significantly lower (p = 0.016 and p = 0.001 respectively) in patients than those in controls. Cox univariate analysis revealed high sTie2 serum level as a risk factor for metastasis and as a borderline significant risk factor for disease related death (p = 0.022 and p = 0.081 respectively). These correlations were independent from tumor stage and grade in a Cox multivariate model (p = 0.016 and p = 0.069). These data indicate that the serum levels of analyzed angiogenic factors do change characteristically in bladder cancer. The soluble extracellular serum level of Tie2 may provide a stage and grade independent diagnostic tool to select a high risk group of bladder cancer patients.

Prognostic Value of Tissue Vascular Endothelial Growth Factor Expression in Bladder Cancer: a Meta-analysis

“…However, conflicting results were showed in other studies regarding the ability of VEGF to predict prognosis in bladder cancer (Suzuki et al, 2005;Nadaoka et al, 2008;Szarvas et al, 2008;Szarvas et al, 2009;Ma et al, 2010;Zaravinos et al, 2012).…”

Angiogenesis and Lymphangiogenesis in Bladder Cancer

“…Other studies on Ang-1 and Ang-2 demonstrated the presence of significantly higher serum levels of Ang-1 in patients with bladder cancer relative to the control; and conversely, Ang-2 and Tie2 levels were significantly lower. (Szarvas, et al, 2009). The same study also showed that high Tie2 serum level was an independent prognostic factor for metastasis in multivariate analysis model that included tumor grade and stage.…”

Effects of Treatment on Angiogenic (Vascular Endothelial Growth Factor-2 and Matrix Metalloproteinase-2) and Antiangiogenic (Endostatin and Thrombospondin-1) Factors in Non-muscle Invasive Bladder Carcinoma

“…Tumor invasion and progression in the bladder represent a multifactorial process affected by imbalance between angiogenic and antiangiogenic factors (9). VEGF and MMP are two of the most important angiogenic factors, while TSP-1 and (10) reported that muscular invasiveness of bladder carcinoma was significantly correlated with serum VEGF level, suggesting that VEGF stimulated proliferation and invasion of tumor via VEGF-2.…”