VEGF, TNF-α 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-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±5.0pg/ml vs. 19.4±3.9pg/ml, p<0.0001) and serum (44.5±6.3pg/ml vs. 22.2±4.3pg/ml, p=0.035). Moreover, EBC VEGF levels were higher in patients with T3–T4 tumor stage compared to T1–T2 (9.3±2.8pg/ml vs. 2.3±0.7pg/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±55.1pg/ml vs. 180.5±14.7pg/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±3.6pg/ml vs. 12.9±1.6pg/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.

Abbreviations: EBC, exhaled breath condensate, VEGF, vascular endothelial growth factor, TNF-α, tumor necrosis factor alpha, ROS, reactive oxygen species, BAL, bronchoalveolar lavage

Keywords: TNF-α, VEGF, 8-Isoprostane, Oxidative stress, Biomarkers, Exhaled breath condensate, Lung cancer