start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=10 article-no= start-page=1602 end-page=1608 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Des-gamma-carboxyl prothrombin is associated with tumor angiogenesis in hepatocellular carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: Hepatocellular carcinoma (HCC) is a hypervascular tumor, and angiogenesis plays an important role in its development. Previously, we demonstrated that des-gamma-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 +/- 3532 mAU/mL) and tumor size (18.4 +/- 9.0 mm) of patients with hypervascular HCC were significantly greater than those with hypovascular HCC (38.7 +/- 80 mAU/mL and 14.6 +/- 5.2 mm, 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-gamma-carboxyl prothrombin production is associated with tumor angiogenesis in HCC. en-copyright= kn-copyright= en-aut-name=MatsubaraMinoru en-aut-sei=Matsubara en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShirahaHidenori en-aut-sei=Shiraha en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KataokaJyunro en-aut-sei=Kataoka en-aut-mei=Jyunro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishinaShin-ichi en-aut-sei=Nishina en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakaokaNobuyuki en-aut-sei=Takaoka en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UemuraMasayuki en-aut-sei=Uemura en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraShinichiro en-aut-sei=Nakamura en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KobayashiYoshiyuki en-aut-sei=Kobayashi en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=2 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=3 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=4 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=5 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=6 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=7 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=8 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=9 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=10 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=11 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=12 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=13 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol en-keyword=des-gamma-carboxyl prothrombin kn-keyword=des-gamma-carboxyl prothrombin en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=intratumoral microvessel density kn-keyword=intratumoral microvessel density en-keyword=kinase insert domain receptor kn-keyword=kinase insert domain receptor END