Department of Gastroenterology, Provincial Hospital affiliated to Shandong University, Jinan, China.
J Clin Pathol. 2012 Sep;65(9):808-14. doi: 10.1136/jclinpath-2012-200721. Epub 2012 Jun 25.
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.
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.
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).
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.
血管内皮生长因子受体 1（VEGFR-1）的激活可促进某些癌细胞的侵袭性。然而，VEGFR-1 的表达及其与肝细胞癌（HCC）临床特征和预后的关系尚不清楚。因此，本研究检测了 VEGFR-1 在 HCC 细胞系和组织标本中的表达模式，以评估 VEGFR-1 在 HCC 预后中的作用。
通过 Western blot 和免疫荧光分别检测细胞系中 VEGFR-1 的表达和定位。用免疫组化检测 135 例根治性切除 HCC 患者组织标本中 VEGFR-1 的表达。用 Kaplan-Meier 分析和 Cox 回归模型确定总生存期（OS）和无复发生存期（RFS）。还分析了 VEGFR-1 表达与临床病理特征之间的关系。
侵袭性更强的 HCC 细胞系中 VEGFR-1 的表达高于侵袭性较弱的细胞系。HCC 组织中 VEGFR-1 的表达明显高于癌旁组织（p<0.001）。根治性切除术后 VEGFR-1 高表达的患者 RFS 和 OS 显著更差（p<0.001）。HCC 组织中 VEGFR-1 的强表达与与进展最相关的最显著临床病理特征相关，低分化是 RFS 和 OS 的独立预后因素（RFS HR 2.397，95%CI 1.686 至 3.409；OS HR 2.44，95%CI 1.518 至 3.922；均 p<0.001）。
VEGFR-1 在 HCC 细胞中的高表达和独特的细胞浆定位与 HCC 的进展和不良预后相关；它可能成为 HCC 患者的一种新的预后标志物。
