Evaluation of tissue and serum levels of VEGF, angiopoietin-1 and angiopoietin-2 in lung cancer

Lung cancer is the commonest fatal malignancy in the developed world, causing more than one million deaths/year. Angiogenesis is an essential process if solids tumors are to grow beyond 2-3 mm3 since diffusion is no longer sufficient to supply the tissue with oxygen and nutrients. Besides numerous angiogenic factors, many antiangiogenic ones are released by solid tumors. Among the regulators of angiogenesis, VEGF is reported to be the most important one. Angiopoetin 1 binds to Tie-2, maintains and stabilizes mature vessels by promoting interaction between endothelial cells and surrounding extracellular matrix. Angiopoetin-2 competitively binds to Tie-2 and antagonizes the stabilizing action of angiopoietin- 1, which results in destabilization of vessels. However some studies have shown that effects of angiopoietin-2 are dose dependent and variable.The aim of this study was to investigate the the serum and tissue levels of VEGF, angiopoietin-1 and angiopoietin-2 in patients with lung cancer. We also evaluated the correlation of tissue and serum parameters with respect to clinicopathological variables.The study was conducted on 34 patients with lung cancer and 32 healthy controls. Preoperative serum and per-op tumor and matched normal tissue VEGF, angiopoietin-1 and angiopoietin-2 levels were determined by ELISA.Serum angiopoietin-2 levels were significantly increased in patient group when compared to the control group (p< 0,001). No significant differences were found for serum VEGF and angiopoietin-1 levels between the two groups. In tumour tissue VEGF level was significantly higher than the normal matched tissue (p<0,001). Angiopoietin-1 and angiopoietin-2 levels were significantly higher in normal lung tissue compared to tumour tissue (p<0,001). When the patients were stratified according to the clinicopathological parameters investigated (gender, age, tumour differentiation, histological type, invasion and lymph node status, T status) serum VEGF level were found to be significantly increased in T3-T4 than T1-T2 subgroups (p= 0,042). Moreover, tumor tissue angiopoietin-1 level was significantly higher in low differentiated group compared to the high differentiated group (p=0.044). Angiopoietin-1 was also found to be higher in patients older than 65 years old than those younger than 65 (p=0,038). A significant positive correlation existed between the serum VEGF and angiopoietin-1 levels (r=0,446; p=0,000). We have found a negative and significant correlation between normal lung tissue angiopoietin-2 and serum VEGF levels (r=-0,400 p=0,019). When the correlations between serum and tissue parameters were investigated, a significant correlation was observed between angiopoietin- 2 levels in normal lung tissue and serum ( r=0,397 p=0,020)In conclusion, our data clearly demonstrated that; VEGF, angiopoietin-1 and 2 are all involved in lung cancer process. We showed, for the first time, the correlation between tissue and serum levels of angiopoietin-2 in lung cancer. We think that, this finding might be the basis for a potent marker in patient evaluation and follow-up and also might enlighten the therapeutic strategies against lung cancer.