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

The aim of the present study was to evaluate the levels of VEGF, 8-isoprostane and TNF-α 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-α 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-α, 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-α, 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-α, 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-α 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.