Serum VEGF and VEGF-C values before surgery and after postoperative treatment in gastric cancer

Abstract

Introduction: Angiogenesis and lymphangiogenesis are essential processes for the formation of blood and lymphatic vessels that allow tumour growth and spread. The binding of VEGF and VEGF-C factors with their receptors (VEGFR2, VEGFR3) in endothelial cells triggers signals that regulate these processes. We compared preoperative serum VEGF and VEGF-C levels with samples obtained after completion of surgery and adjuvant treatment in patients with gastric cancer. In addition, we determined the prognostic value and relationship to survival of serum VEGF and VEGF-C levels. Methods: We used a prospective cohort study of 59 gastric cancer patients who underwent surgery. Serum VEGF and VEGF-C were measured by enzyme-linked immunosorbent assay (ELISA) the day before surgery and 6 months later, after completion of adjuvant treatment. Results: Serum VEGF values decreased after treatment in patients with resectable tumours (mean ± SD) (405.42 ± 298.38 vs. 306.38 ± 212.47 pg/ml; p < 0.01), poorly differentiated and undifferentiated tumours (G3, G4) (438 ± 339.71 vs. 322.47 ± 210.71 pg/ml; p = 0.01), locally advanced gastric tumours (T4 stage) (424.27 ± 323.08 vs. 333.62 ± 221.72 pg/ml; p = 0.03) and tumours with a greater number of involved regional lymph nodes (N3) (442.38 ± 311.52 vs. 337.4 ± 203.64 pg/ml; p = 0.04). Serum preoperative VEGF values over 761 pg/ml were associated with shorter patient survival. The mean overall survival time for patients with serum VEGF levels higher than 761 pg/ml was 7 ± 2.99 months (95 % CI 1.14-12.86) while for patients with serum VEGF levels of less than 761 pg/ml was 21.18 ± 2.88 (95 % CI 15.54-26.83) The mean disease-specific survival time for patients with serum VEGF levels higher than 761 pg/ml was 6.25 ± 2.53 months (95 % CI 1.29-11.21) while for patients with serum VEGF levels of less than 761 pg/ml was 27.57 ± 3.45 (95 % CI 20.80-34.35). Multivariate analysis identified preoperative serum VEGF levels as an independent prognostic factor (HR = 0.144; p = 0.03). Conclusions: Serum VEGF levels decreased after the completion of treatment in patients with resected tumours, suggesting VEGF tracking may be useful in monitoring progression. Preoperative measurement of serum VEGF may help us identify patients with a poor prognosis. © 2012 Federación de Sociedades Españolas de Oncología (FESEO).