Oncotarget

Clinical Research Papers:

Overexpression of platelet-derived growth factor receptor alpha promotes tumor progression and indicates poor prognosis in hepatocellular carcinoma

Tao Wei _, Li-Na Zhang, Yi Lv, Xiao-Ya Ma, Lei Zhi, Chang Liu, Feng Ma and Xu-Feng Zhang

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Oncotarget. 2014; 5:10307-10317. https://doi.org/10.18632/oncotarget.2537

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Abstract

Tao Wei1,*,4, Li-Na Zhang2,*, Yi Lv1, Xiao-Ya Ma2, Lei Zhi3, Chang Liu1, Feng Ma1, Xu-Feng Zhang1

1 Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, the 1st Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi Province, 710061, China

2 Department of Pharmacy, the 2nd Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi Province, 710004, China

3 Department of General Surgery, General Hospital of Ningxia Medical College, Yinchuan, Ningxia Hui Autonomous Region, 750004, China

4 Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China

*These authors contributed equally to this work

Correspondence to:

Xu-Feng Zhang, email: [email protected]

Keywords: Platelet-derived growth factor receptor alpha, Hepatocellular carcinoma, survival, metastasis, CD31

Received: May 09, 2014     Accepted: September 29, 2014     Published: October 17, 2014

ABSTRACT

Dysregulation of platelet-derived growth factor receptor alpha (PDGFRα) has been documented in various cancers. However, its role in hepatocellular carcinoma (HCC) remains unknown. We and others have examined that upregulation of PDGFRα might be involved in hepatocarcinogenesis. Here, we report that PDGFRα plays a critical role in HCC progression and prognosis. The expression of PDGFRα was markedly higher in human HCC compared to adjacent liver tissues. Although PDGFRA mRNA was decreased in HCC, PDGF-A mRNA was dramatically increased in HCC. Overexpression of PDGFRα was strongly correlated with microvessel density (MVD) of HCC (p<0.05), as well as macroscopic vascular invasion of the tumors (p<0.05). HCC patients with high PDGFRα expression displayed a shorter overall survival and a higher recurrence rate than those with low PDGFRα expression (p<0.05, respectively). Additionally, stable overexpression of PDGFRα in hepatoma cells promoted cell proliferation, migration, invasion and epithelial-mesenchymal transition in vitro. Similarly, an in vivo assay showed that PDGFRα overexpression in hepatoma cells exhibited remarkably tumorigenic potential in tumor size and weight in vivo, which displayed markedly elevated MVD than controls. Thus, our study provided the evidence that PDGFRα may serve as a candidate prognostic marker and a novel therapeutic target for HCC.


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