TY - JOUR
T1 - Des-γ-carboxyl prothrombin is associated with tumor angiogenesis in hepatocellular carcinoma
AU - Matsubara, Minoru
AU - Shiraha, Hidenori
AU - Kataoka, Jyunro
AU - Iwamuro, Masaya
AU - Horiguchi, Shigeru
AU - Nishina, Shin Ichi
AU - Takaoka, Nobuyuki
AU - Uemura, Masayuki
AU - Takaki, Akinobu
AU - Nakamura, Shinichiro
AU - Kobayashi, Yoshiyuki
AU - Nouso, Kazuhiro
AU - Yamamoto, Kazuhide
PY - 2012/10
Y1 - 2012/10
N2 - Background and Aim: Hepatocellular carcinoma (HCC) is a hypervascular tumor, and angiogenesis plays an important role in its development. Previously, we demonstrated that des-γ-carboxyl prothrombin (DCP) promotes both cell proliferation and migration of human umbilical vein endothelial cells (HUVECs) by inducing the autophosphorylation of kinase insert domain receptor (KDR). In the present study, DCP-associated tumor angiogenesis was assessed by comparing hypovascular and common hypervascular HCC. Methods: The solitary HCCs of 827 patients were classified into two groups according to the tumor density at the arterial phase of a dynamic computed tomography scan; the initial clinical data of patients with the hyper- and hypovascular types were compared. The HCC tissues from 95 tumors were analyzed by immunohistochemical staining for DCP and phosphorylated KDR, and intratumoral microvessel density (MVD) was analyzed to evaluate microvessel angiogenesis. Results: The serum DCP levels (320±3532mAU/mL) and tumor size (18.4±9.0mm) of patients with hypervascular HCC were significantly greater than those with hypovascular HCC (38.7±80mAU/mL and 14.6±5.2mm, P<0.001). Immunohistochemical analysis revealed that the expressions of DCP and phospho-KDR were significantly greater in hypervascular HCC (71.4% and 31.0%, respectively) than in hypovascular HCC (7.6% and 5.7%, respectively). Intratumoral MVD was significantly correlated with DCP (r=0.48, P<0.0001). Conclusions: des-γ-carboxyl prothrombin production is associated with tumor angiogenesis in HCC.
AB - Background and Aim: Hepatocellular carcinoma (HCC) is a hypervascular tumor, and angiogenesis plays an important role in its development. Previously, we demonstrated that des-γ-carboxyl prothrombin (DCP) promotes both cell proliferation and migration of human umbilical vein endothelial cells (HUVECs) by inducing the autophosphorylation of kinase insert domain receptor (KDR). In the present study, DCP-associated tumor angiogenesis was assessed by comparing hypovascular and common hypervascular HCC. Methods: The solitary HCCs of 827 patients were classified into two groups according to the tumor density at the arterial phase of a dynamic computed tomography scan; the initial clinical data of patients with the hyper- and hypovascular types were compared. The HCC tissues from 95 tumors were analyzed by immunohistochemical staining for DCP and phosphorylated KDR, and intratumoral microvessel density (MVD) was analyzed to evaluate microvessel angiogenesis. Results: The serum DCP levels (320±3532mAU/mL) and tumor size (18.4±9.0mm) of patients with hypervascular HCC were significantly greater than those with hypovascular HCC (38.7±80mAU/mL and 14.6±5.2mm, P<0.001). Immunohistochemical analysis revealed that the expressions of DCP and phospho-KDR were significantly greater in hypervascular HCC (71.4% and 31.0%, respectively) than in hypovascular HCC (7.6% and 5.7%, respectively). Intratumoral MVD was significantly correlated with DCP (r=0.48, P<0.0001). Conclusions: des-γ-carboxyl prothrombin production is associated with tumor angiogenesis in HCC.
KW - Des-γ-carboxyl prothrombin
KW - Hepatocellular carcinoma
KW - Intratumoral microvessel density
KW - Kinase insert domain receptor
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U2 - 10.1111/j.1440-1746.2012.07173.x
DO - 10.1111/j.1440-1746.2012.07173.x
M3 - Article
C2 - 22554292
AN - SCOPUS:84866550659
VL - 27
SP - 1602
EP - 1608
JO - Journal of Gastroenterology and Hepatology (Australia)
JF - Journal of Gastroenterology and Hepatology (Australia)
SN - 0815-9319
IS - 10
ER -