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Expression and prognostic significance of vascular endothelial growth factor receptor 1 in hepatocellular carcinoma
  1. Tao Li1,
  2. Yuhua Zhu1,
  3. Cheng-yong Qin1,
  4. Zhen Yang1,
  5. Aiju Fang2,
  6. Shifeng Xu3,
  7. Wanhua Ren1
  1. 1Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan, China
  2. 2Department of Pathology, Shandong Jiaotong Hospital, Jinan, China
  3. 3Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, China
  1. Correspondence to Professor Wanhua Ren, 324#, Jing 5 Road, Jinan, China; rwanhua{at}


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.

  • Cancer
  • gastroenterology
  • haematopathology
  • hepatitis
  • hepatocellular carcinoma
  • HIV
  • Hodgkins disease
  • immunohistochemistry
  • invasion
  • liver cancer
  • liver disease
  • oncology
  • vascular endothelial growth factor receptor 1

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  • Additional tables are published online only. To view these files please visit the journal online (

  • Funding This study was supported by Shandong Outstanding Youth Science Fund (no. 2007BS03005).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval The study was approved by the Ethics Committee of Provincial Hospital affiliated to Shandong University.

  • Provenance and peer review Not commissioned; externally peer reviewed.