Upregulation of vasohibin-1 expression with angiogenesis and poor prognosis of hepatocellular carcinoma after curative surgery.

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.