Wei Tao, Zhang Li-Na, Lv Yi, Ma Xiao-Ya, Zhi Lei, Liu Chang, Ma Feng, Zhang Xu-Feng
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. Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
Department of Pharmacy, the 2nd Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710004, China.
Oncotarget. 2014 Nov 15;5(21):10307-17. doi: 10.18632/oncotarget.2537.
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.
血小板衍生生长因子受体α（PDGFRα）的失调在多种癌症中都有记录。然而，其在肝细胞癌（HCC）中的作用仍不清楚。我们和其他人已经研究发现，PDGFRα的上调可能参与肝癌发生。在此，我们报告PDGFRα在HCC进展和预后中起关键作用。与相邻肝组织相比，PDGFRα在人类HCC中的表达明显更高。虽然HCC中PDGFRA mRNA减少，但PDGF - A mRNA在HCC中显著增加。PDGFRα的过表达与HCC的微血管密度（MVD）密切相关（p<0.05），也与肿瘤的宏观血管侵犯密切相关（p<0.05）。与低PDGFRα表达的HCC患者相比，高PDGFRα表达的患者总生存期更短，复发率更高（分别为p<0.05）。此外，在肝癌细胞中稳定过表达PDGFRα可促进体外细胞增殖、迁移、侵袭和上皮 - 间质转化。同样，体内实验表明，肝癌细胞中PDGFRα过表达在体内肿瘤大小和重量方面具有显著的致瘤潜力，其MVD比对照组明显升高。因此，我们的研究提供了证据表明PDGFRα可能作为HCC的候选预后标志物和新的治疗靶点。
