Platelet activation and vascular endothelial growth factor 165 release in hepatocellular cancer.
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.
Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele, Rome, Italy. patrizia.ferroni@sanraffaele.it
Patrizia
P
Ferroni
Antonella
A
Spila
Roberta
R
D'Alessandro
Francesca
F
Martini
Francesca
F
Iacovone
Giuseppe M
GM
Ettorre
Giovanni
G
Vennarecci
Roberto
R
Santoro
Claudio
C
Puoti
Fiorella
F
Guadagni
D001774:Blood Chemical Analysis; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000378:metabolism*
D019007:P-Selectin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A