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

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Abstract

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.

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Abbreviations

HCC:

Hepatocellular carcinoma

VEGFR-1:

Vascular endothelial growth factor receptor-1

TNM:

Tumor-node metastasis

MMP-9:

Matrix metalloproteinase-9

TMA:

Tissue microarray

ROC:

Receiver operating characteristic

AFP:

α-fetoprotein

EMT:

Epithelial–mesenchymal transition

HBsAg:

Hepatitis B s antigen

OS:

Overall survival

RFS:

Recurrence-free survival

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Acknowledgments

We are grateful to Dr. Edward C. Mignot for professional linguistic advice. We are also grateful to Professor Ling Gao (Central Laboratory of Provincial Hospital Affiliated to Shandong University, Jinan, China) for helpful discussion regarding this research area. This study was supported by Shandong Outstanding Youth Science Fund (No. 2007BS03005).

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Authors and Affiliations

  1. Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324#, Jing 5 Road, Jinan, 250021, Shandong, People’s Republic of China

    Tao Li, Yuhua Zhu, Wanhua Ren, Zhen Yang & Chengyong Qin

  2. Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, 324#, Jing 5 Road, Jinan, 250021, Shandong, People’s Republic of China

    Shifeng Xu

  3. Department of Pathology, Shandong Jiaotong Hospital, 12#, Wuyingshanzhong Road, Jinan, 250031, Shandong, People’s Republic of China

    Aiju Fang

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  1. Tao Li
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Correspondence to Chengyong Qin.

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Li, T., Zhu, Y., Ren, W. et al. High co-expression of vascular endothelial growth factor receptor-1 and Snail is associated with poor prognosis after curative resection of hepatocellular carcinoma. Med Oncol 29, 2750–2761 (2012). https://doi.org/10.1007/s12032-012-0160-9

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  • DOI: https://doi.org/10.1007/s12032-012-0160-9

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