VEGF, TNF-alpha 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-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+/-0.7pg/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+/-55.1 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.
Dalaveris
Eleftherios
E
Respiratory Medicine Department, University of Thessaly Medical School, University Hospital of Larissa, Larissa 41110, Greece.
Kerenidi
Theodora
T
Katsabeki-Katsafli
Alexandra
A
Kiropoulos
Theodoros
T
Tanou
Kalliopi
K
Gourgoulianis
Konstantinos I
KI
Kostikas
Konstantinos
K
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001944:Breath Tests; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D045853:Exhalation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
D014408:Biomarkers, Tumor; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost