Vascular endothelial growth factor measured in platelet poor plasma allows optimal separation between cancer patients and volunteers: A key to study an angiogenic marker in vivo?

Abstract

Background: Serum VEGF levels are elevated in cancer patients and are used as a tumor marker in different malignancies. We have measured VEGF levels in different blood compartments in cancer patients and healthy volunteers in order to assess the most suitable way of processing blood for measuring VEGF as a marker of tumor-angiogenesis. Patients and methods: VEGF concentrations were analyzed by an enzyme-linked immunosorbent assay in serum (VEGFs), EDTA plasma (VEGF(EDTA)), citrated plasma (VEGF(C)), CTAD-plasma (VEGF(CTAD)), platelet poor plasma (VEGF(PPP)), platelet rich plasma after induction of platelet activation (VEGF(PRP)). Platelet activation was assessed by measuring PF4 concentrations in different plasma samples. Results: We observed higher VEGFs (P = 0.0027), VEGF(EDTA) (P = 0.003) and VEOF(PPP) (P = 0.0007) levels in cancer patients than in volunteers; VEGF(PRP) concentrations showed no significant difference (P = 0.208). Analysis of the correlation between VEGF(plt) and VEGF(S) in cancer patients showed a similar correlation in a comparable VEGF(S) concentration range as in the volunteers. When comparing VEGF(C) to VEGF(CTAD), we find significantly higher VEGF and PF4 levels in citrated plasma (VEGF: P = 0.00019; PF4: P = 0.00023). Conclusions: It is likely that VEGF(S) in cancer patients encompass platelet-delivered VEGF and VEGF from other sources, notably from (neo)-angiogenesis in tumoral tissue. The best discrimination between volunteers and cancer patients was observed in PPP. As generating plasma can induce platelet activation, with consequent VEGF release from platelets, we suggest that to assess free circulating VEGF, CTAD plasma should be used.