Iavarone M, Lampertico P, Iannuzzi F, Manenti E, Donato M F, Arosio E, Bertolini F, Primignani M, Sangiovanni A, Colombo M
AM & A Migliavacca Center for Liver Diseases, Department of Gastroenterology and Endocrinology, IRCCS Maggiore Hospital Fondazione Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy.
J Viral Hepat. 2007 Feb;14(2):133-9. doi: 10.1111/j.1365-2893.2006.00782.x.
Vascular endothelial growth factor (VEGF) is involved in both development and progression of several epithelial tumours, but its role in hepatocellular carcinoma (HCC) is unclear. Assessment of liver and blood levels of VEGF may provide further insights on angiogenesis in HCC. Tissue mRNA of VEGF-165, VEGF-189 and their receptor KDR was assessed by a semi-quantitative retro-transcriptase polymerase chain reaction, and expressed as target transcript/beta-actin ratio, in 29 patients with HCC, 26 with cirrhosis and 15 with chronic hepatitis. VEGF-165 was also measured by ELISA in plasma samples obtained from both hepatic and femoral veins in additional 58 patients, including 15 with HCC. The liver expression of mRNA of VEGF-165, VEGF-189 and KDR was higher in HCC than in chronic liver diseases (1.54 +/- 0.89 vs 0.62 +/- 0.47, P < 0.0001; 1.09 +/- 0.65 vs 0.64 +/- 0.54, P = 0.003; 1.30 +/- 1.09 vs 0.69 +/- 0.72, P = 0.014). VEGF-165 was higher in HCC tissue than in extra-tumoural tissues (1.44 +/- 0.31 vs 1.03 +/- 0.21, P = 0.0009) and in the cirrhotic tissue of HCC patients than in HCC-free cirrhosis (1.03 +/- 0.23 vs 0.45 +/- 0.45, P = 0.0002). Tissue VEGF-189 mRNA inversely correlated with tumour size and degree of tumour cell proliferation. The hepatic and femoral vein levels of VEGF-165 protein were significantly higher in HCC patients than in cirrhotic patients (66.7 +/- 57.1 vs 24.2 +/- 16.4 pg/mL, P = 0.0001 and 37.1 +/- 42.2 vs 13.5 +/- 9.6 pg/mL, P = 0.001). There was a gradient of VEGF-165 between hepatic and femoral veins in both HCC and cirrhosis. In conclusion, VEGF appears to be involved in the development of HCC and it could be a predictor of HCC development in patients with cirrhosis.
血管内皮生长因子（VEGF）参与多种上皮性肿瘤的发生和发展，但其在肝细胞癌（HCC）中的作用尚不清楚。评估肝脏和血液中VEGF水平可能有助于进一步了解HCC中的血管生成情况。采用半定量逆转录聚合酶链反应评估了29例HCC患者、26例肝硬化患者和15例慢性肝炎患者的VEGF-165、VEGF-189及其受体KDR的组织mRNA，并以靶转录本/β-肌动蛋白比值表示。还采用酶联免疫吸附测定法（ELISA）检测了另外58例患者（包括15例HCC患者）肝静脉和股静脉血浆样本中的VEGF-165。HCC患者肝脏中VEGF-165、VEGF-189和KDR的mRNA表达高于慢性肝病患者（分别为1.54±0.89对0.62±0.47，P<0.0001；1.09±0.65对0.64±0.54，P=0.003；1.30±1.09对0.69±0.72，P=0.014）。VEGF-165在HCC组织中的表达高于肿瘤外组织（1.44±0.31对1.03±0.21，P=0.0009），在HCC患者的肝硬化组织中的表达高于无HCC的肝硬化患者（1.03±0.23对0.45±0.45，P=0.0002）。组织VEGF-189 mRNA与肿瘤大小和肿瘤细胞增殖程度呈负相关。HCC患者肝静脉和股静脉中VEGF-165蛋白水平显著高于肝硬化患者（分别为66.7±57.1对24.2±16.4 pg/mL，P=0.0001；37.1±42.2对13.5±9.6 pg/mL，P=0.001）。HCC和肝硬化患者肝静脉和股静脉之间的VEGF-165均存在梯度差异。总之，VEGF似乎参与了HCC的发生，并且可能是肝硬化患者HCC发生的一个预测指标。
