Expression and prognostic significance of vascular endothelial growth factor receptor 1 in hepatocellular carcinoma.
OBJECTIVE
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.
Department of Gastroenterology, Provincial Hospital affiliated to Shandong University, Jinan, China.
Tao
T
Li
Yuhua
Y
Zhu
Cheng-yong
CY
Qin
Zhen
Z
Yang
Aiju
A
Fang
Shifeng
S
Xu
Wanhua
W
Ren
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D005455:Fluorescent Antibody Technique; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
D014408:Biomarkers, Tumor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1