VEGF, TNF-alpha and 8-isoprostane levels in exhaled breath condensate and serum of patients with lung cancer

Abstract

The aim of the present study was to evaluate the levels of VEGF, 8-isoprostane and TNF-alpha in EBC and serum of patients with primary lung cancer prior to the initiation of any treatment, in order to evaluate their possible diagnostic role. Furthermore, associations between VEGF, 8-isoprostane and TNF-alpha levels in EBC and serum with clinicopathologic factors were investigated. We enrolled 30 patients with lung cancer (mean age 65.2 +/- 10.5 years) and 15 age and gender-matched healthy smokers as controls. Serum and EBC were collected before any treatment. TNF-alpha, VEGF and 8-isoprostane levels in EBC and serum were analyzed by an immunoenzymatic method (ELISA). A statistically significant difference was observed between lung cancer patients and the control group regarding the values of TNF-alpha, both in EBC (52.9 +/- 5.0 pg/ml vs. 19.4 +/- 3.9 pg/ml, p < 0.0001) and serum (44.5 +/- 6.3 pg/ml vs. 22.2 +/- 4.3 pg/ml, p = 0.035). Moreover, EBC VEGF levels were higher in patients with T3-T4 tumor stage compared to T1-T2 (9.3 +/- 2.8 pg/ml vs. 2.3 +/- 0.7 pg/ml, p = 0.047). A statistically significant correlation was also observed between serum and EBC values of VEGF (r = 0.52, p = 0.019). In addition, serum levels of VEGF were higher in lung cancer patients than in controls (369.3 +/- 55.1 pg/ml vs. 180.5 +/- 14.7 pg/ml, p = 0.046). VEGF serum levels were also found higher in patients with advanced stage of disease (IIIB-IV) and distant nodal metastasis (N2-N3). No differences were observed in 8-isoprostane in EBC between lung cancer patients and controls. In contrast, serum 8-isoprostane levels were higher in lung cancer patients compared to controls (24.9 +/- 3.6 pg/ml vs. 12.9 +/- 1.6 pg/ml, p = 0.027) and were higher in patients with advanced disease. All three biomarkers presented acceptable reproducibility in the EBC on two consecutive days. In conclusion, we have shown that TNF-alpha, VEGF and 8-isoprostane are elevated in the serum of lung cancer patients and increased serum VEGF and 8-isoprostane levels are related to advanced disease. In EBC, increased TNF-alpha levels were observed in lung cancer patients, whereas increased VEGF levels were observed in advanced T-stage. Further longitudinal studies are warranted for the evaluation of the prognostic role of these biomarkers in lung cancer. (C) 2008 Elsevier Ireland Ltd. All rights reserved.