High co-expression of vascular endothelial growth factor receptor-1 and Snail is associated with poor prognosis after curative resection of hepatocellular carcinoma

VEGFR-1-mediated signaling promotes invasiveness by direct tumor activation in some cancers. However, VEGFR-1 expression and its relationship with clinical features and prognosis in HCC remained unclear. Overexpression of Snail is common in HCC and associated with poorer prognosis. Therefore, expression of VEGFR-1 and Snail was investigated in HCC cell lines and tissue specimens in our study, and special attention was paid to evaluating the role of VEGFR-1 expression in prognosis of HCC. Western blot and immunofluorescence were used to detect expression of VEGFR-1, Snail and MMP-9 in 4 HCC cell lines, respectively. Moreover, expression of these proteins was confirmed on the samples from 95 HCC patients who underwent curative resection using immunohistochemistry. ROC and survival analysis determined the predictive values of parameters and the association with survival. HCC cell lines with a higher VEGFR-1 expression were more invasive. Both VEGFR-1 and Snail expressions were significantly higher in HCC tissues than in non-cancerous tissues. High-expression VEGFR-1 and Snail, associated with adverse clinical features, were independent prognostic factors for RFS and OS (P = 0.023 and P = 0.044, respectively). Positive correlation was found between VEGFR-1 and Snail or MMP-9 (r = 0.418 and r = 0.232, respectively, P < 0.05 for both) in cancerous tissues. The combination of VEGFR-1 and Snail gave a better power to predict patients' recurrence and death (P < 0.001 for both). High VEGFR-1 expression, distinctively expressed in the cytomembrane of HCC cells, was associated with HCC progression and worse outcome. High co-expression of VEGFR-1 and Snail may be a novel prognostic marker for HCC, especially in recurrence.