Expression and prognostic significance of vascular endothelial growth factor receptor 1 in hepatocellular carcinoma

Abstract

Aims: Activation of vascular endothelial growth factor receptor 1 (VEGFR-1) promotes invasiveness in some cancer cells. However, VEGFR-1 expression and its relationship with clinical features and prognosis in hepatocellular carcinoma (HCC) remain unclear. Therefore, this study investigated the expression pattern of VEGFR-1 in HCC cell lines and tissue specimens in order to evaluate the role of VEGFR-1 in prognosis of HCC.

Methods: Expression and localisation of VEGFR-1 in cell lines were determined by western blot and immunofluorescence, respectively. Expression of VEGFR-1 in tissue specimens from 135 HCC patients with curative resections was determined by immunohistochemistry. Overall survival (OS) and recurrence-free survival (RFS) were determined by Kaplan-Meier analysis and a Cox regression model. The relationships between VEGFR-1 expression and clinicopathological features were also analysed.

Results: VEGFR-1 expression in more invasive HCC cell lines is higher than that in less invasive cell lines. VEGFR-1 expression in HCC tissues was significantly higher than that in peritumoral tissues (p<0.001). Patients with high expression of VEGFR-1 had significantly worse RFS and OS after curative resections (p<0.001). Strong expression of VEGFR-1 in HCC tissues was correlated with the most prominent clinicopathological features associated with progression, and poor differentiation was an independent prognosticator for RFS and OS (RFS HR 2.397, 95% CI 1.686 to 3.409; OS HR 2.44, 95% CI 1.518 to 3.922; p<0.001 for both).

Conclusions: High expression and distinctive cytomembrane localisation of VEGFR-1 in HCC cells is associated with HCC progression and worse outcome; it may serve as a novel prognostic marker for patients with HCC.