Division of Hepatogastroenterology, Department of Internal Medicine, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan, 250021, Shandong Province, Peoples Republic of China.
Med Oncol. 2012 Dec;29(4):2727-36. doi: 10.1007/s12032-011-0106-7. Epub 2011 Nov 19.
Vasohibin-1 has recently been found and is known as an endogenous angiogenesis inhibitor, but the role of vasohibin-1 in hepatocellular carcinoma (HCC) is unknown. This study investigated the expression pattern of vasohibin-1, its correlation with clinicopathological features, and its potential role in tumor angiogenesis and prognosis of HCC. Expression of vasohibin-1, vascular endothelial growth factor-A (VEGF-A), and intratumoral microvessel density (MVD, labeled by CD34) were assessed by immunohistochemistry in 117 HCC specimens and adjacent nontumor liver tissues (ANLT). Correlation between vasohibin-1 and VEGF-A, MVD, and clinicopathological features was then investigated. Prognostic value of these factors was determined using Kaplan-Meier analysis and a Cox proportional hazards regression model. Cytoplasm high expression of vasohibin-1 was detected in 38.5% (45/117) of the HCC tissues, which was significantly higher than that in 16.2% (19/117) of ANLT (P<0.001). Vasohibin-1 was statistically correlated with VEGF-A, MVD, and microvascular invasion in HCC (P=0.014, 0.035, and 0.002, respectively). Patients with vasohibin-1 high expression had significantly poor disease-free survival (DFS) and overall survival (OS) at 5 years after curative hepatectomy (P<0.001 for each). Multivariate analysis confirmed that vasohibin-1 high expression was an independent prognosticator for unfavorable DFS (HR=2.554, P<0.001) and OS (HR=2.232, P=0.002), along with VEGF-A and TNM stage. Upregulation of vasohibin-1 expression is associated with angiogenesis and poor prognosis of HCC. Vasohibin-1 and VEGF-A are the most important factors influencing the dismal prognosis based on the modulation of angiogenesis in HCC, which provides a rational approach for treatment in the future.
血管抑素-1 最近被发现，被认为是一种内源性血管生成抑制剂，但它在肝细胞癌 (HCC) 中的作用尚不清楚。本研究通过免疫组化方法检测了血管抑素-1 在 117 例 HCC 标本和相邻非肿瘤肝组织 (ANLT) 中的表达模式，及其与临床病理特征的相关性，并探讨了其在肿瘤血管生成和 HCC 预后中的作用。然后研究了血管抑素-1 与 VEGF-A、MVD 及临床病理特征的相关性。通过 Kaplan-Meier 分析和 Cox 比例风险回归模型确定这些因素的预后价值。HCC 组织中细胞质高表达血管抑素-1 的比例为 38.5%（45/117），明显高于 ANLT 的 16.2%（19/117）（P<0.001）。血管抑素-1 与 HCC 中的 VEGF-A、MVD 和微血管侵犯呈统计学相关（P=0.014、0.035 和 0.002）。根治性肝切除术后 5 年，血管抑素-1 高表达患者的无病生存率（DFS）和总生存率（OS）明显较差（P<0.001）。多因素分析证实，血管抑素-1 高表达是不利 DFS（HR=2.554，P<0.001）和 OS（HR=2.232，P=0.002）的独立预后因素，与 VEGF-A 和 TNM 分期有关。血管抑素-1 表达上调与 HCC 血管生成和不良预后有关。血管抑素-1 和 VEGF-A 是影响 HCC 预后不良的最重要因素，基于 HCC 血管生成的调节，为未来的治疗提供了合理的方法。
