title: Upregulation of vasohibin-1 expression with angiogenesis and poor prognosis of hepatocellular carcinoma after curative surgery.
abstract: 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.
authors.affiliation: 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.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Tian
authors.forename: Chunqing
authors.initials: C
authors.lastname: Zhang
authors.forename: Qiangxiu
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018797:Cell Cycle Proteins / Q000032:analysis / Q000502:physiology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000209:etiology*; D011379:Prognosis; D016016:Proportional Hazards Models; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D018797:Cell Cycle Proteins; C493181:VASH1 protein, human; D042461:Vascular Endothelial Growth Factor A
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