去γ-羧基凝血酶原与肝细胞癌中的肿瘤血管生成有关。

Des-γ-carboxyl prothrombin is associated with tumor angiogenesis in hepatocellular carcinoma.

机构信息

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.

出版信息

J Gastroenterol Hepatol. 2012 Oct;27(10):1602-8. doi: 10.1111/j.1440-1746.2012.07173.x.

DOI:10.1111/j.1440-1746.2012.07173.x

PMID:22554292

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-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 ± 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-γ-carboxyl prothrombin production is associated with tumor angiogenesis in HCC.

摘要

背景与目的

肝细胞癌（HCC）是一种富血管肿瘤，血管生成在其发展中起着重要作用。先前，我们已经证明去γ-羧基凝血酶原（DCP）通过诱导激酶插入结构域受体（KDR）的自身磷酸化，促进人脐静脉内皮细胞（HUVEC）的细胞增殖和迁移。在本研究中，通过比较低血管形成和常见高血管形成 HCC，评估 DCP 相关的肿瘤血管生成。

方法

根据动态 CT 扫描动脉期肿瘤密度，将 827 例 HCC 患者分为两组；比较高血管和低血管型患者的初始临床数据。对 95 例 HCC 组织进行 DCP 和磷酸化 KDR 的免疫组织化学染色分析，并分析肿瘤内微血管密度（MVD）以评估微血管血管生成。

结果

高血管形成 HCC 患者的血清 DCP 水平（320±3532 mAU/mL）和肿瘤大小（18.4±9.0 mm）明显大于低血管形成 HCC 患者（38.7±80 mAU/mL 和 14.6±5.2 mm，P<0.001）。免疫组织化学分析显示，DCP 和磷酸化 KDR 的表达在高血管形成 HCC 中明显高于低血管形成 HCC（分别为 71.4%和 31.0%，分别为 7.6%和 5.7%）。肿瘤内 MVD 与 DCP 显著相关（r=0.48，P<0.0001）。