Plasma levels of VEGF-A and VEGFR-2 in advanced NSCLC.

Abstract

10623 Background: VEGF ligands and receptors have an important role in tumor angiogenesis. An increased expression of these angiogenic factors in tumor or serum/plasma is associated with metastasis and poor prognosis. The aim of this study is to investigate the usefulness of the quantification of soluble VEGF-A and VEGFR-2 as biomarkers in advanced NSCLC. Methods: We studied 458 advanced NSCLC (stages IIIB-IV) patients treated with cisplatin and docetaxel and 89 healthy age-matched controls. Blood samples were collected before chemotherapy and VEGF-A and VEGFR-2 protein levels were determined by ELISA. All statistical analyses were considered significant at p ≤ 0.05. Results: VEGF-A and VEGFR-2 levels were significantly higher in patients than controls; VEGF-A: 105.92 ± 5.30 pg/mL vs 26.17 ± 5.35 pg/mL, respectively; p < 0.0001; and VEGFR-2: 8,346 ± 120 pg/mL vs 6,903 ± 144 pg/mL, respectively; p < 0.0001). The area under the ROC curve was 0.858 for VEGF-A and 0.744 for VEGFR-2, indicating that both variables are suitable biomarkers for discrimination between the groups. Patients with high VEGFR-2 plasma levels (75 percentile) show a significantly longer time to progression (TTP, p = 0.029). On the other hand, high levels of soluble VEGF-A (75 percentile) correlates with a poor overall survival (OS, p = 0.026). A subgroup characterized by a combination of high levels of soluble VEGF-A and low levels of soluble VEGFR-2 had the worse prognosis regarding TTP (p = 0.042) and OS (p = 0.003), when compared with other possible combinations of markers. Conclusions: In advanced NSCLC, soluble levels of VEGF-A and VEGFR-2 are significantly higher in patients than age-matched controls. The combination of high plasma VEGF-A and low VEGFR-2 identified a NSCLC subgroup with a poorer prognosis, that may benefit from additional antiangiogenic therapy. No significant financial relationships to disclose.