Platelet activation and vascular endothelial growth factor 165 release in hepatocellular cancer

Abstract

Background: Vascular endothelial growth factor (VEGF₁₆₅) is stored, transported and released by platelets. Platelet functional abnormalities have been described in patients with hepatocellular carcinoma (HCC). Thus, this study was designed to investigate the behavior of VEGF₁₆₅ with respect to platelet activation in HCC.

Methods: Plasma and serum VEGF₁₆₅ and plasma sP-selectin levels were analyzed in patients with HCC (n=70) or cirrhosis (n=45) and control subjects (n=70). Given the thrombocytopenia that characterizes both HCC and cirrhotic patients, plasma VEGF₁₆₅ and sP-selectin as well as serum VEGF (plt-VEGF₁₆₅-load) levels were normalized by platelet counts.

Results: Median concentrations of plasma VEGF₁₆₅/platelet (p=0.002) and sP-selectin/platelet (p<0.0001) were higher in HCC or cirrhotic patients compared to controls. Moreover, sP-selectin/platelet was the only independent variable predictive of plasma VEGF₁₆₅/platelet at multivariate analysis (p<0.0001). Conversely, plt-VEGF₁₆₅-load correlated with tumor diameter (p<0.05) but not with sP-selectin/platelet and was an independent predictor for 5year overall survival (p=0.012).

Conclusions: The results obtained are suggestive for VEGF₁₆₅ release by tumor in HCC. It is plt-VEGF₁₆₅-load, but not plasma VEGF₁₆₅ or serum VEGF₁₆₅ that is an independent predictor for overall survival of HCC patients.