四种血管特异生长因子mRNA与肝癌发生和门静脉瘤栓形成的关系

Correlation of four vascular specific growth factors mRNA with carcionogenesis and portal vein tumor thrombus formation in human hepatocellular carcinoma

目的:探讨血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)、促血管生成素2(angiopoietin,Ang2)、ephrinB2和内分泌腺源血管内皮生长因子(endocrinegland-derivedvascularendothelialgrowthfactor,EG-VEGF)在肝癌发生和门静脉瘤栓(PVTT)形I中的作用。方法:收集手术切除的无门静脉主干瘤栓的肝癌标本(A组)54例、伴门静脉主干瘤栓的肝癌标本(B组)9例和肝英化组织(C组)、正常肝组织(D组)各10例。用RT-PCR法检测标本中VEGF、Ang2、ephrinB2和EG-VEGF的表达。用免疫组织化学方法检测内皮细胞的标志分子CD34,并计数微血管密度(microvesseldensity,MVD),比较四组标本中各因子的表达和MVD水平。结果:A、B、C和D组的MVD分别为146·69±77·79、214·07±54·41、32·85±8·49和34·83±8·29,差异有统计学意义,F=19·77,P=0·000,且A组的MVD低于B组,P=0·006,高于C组,P=0·000。VEGF165、VEGF189、Ang2和EG-VEGFmRNA在四组标本中表达的差异有统计学意义,且VEGF165、Ang2和EG-VEGFmRNA在A、C两组和A、B两组内表达的差异有统计学意义(P值都<0·05或0·01)。肝癌中VEGF165、VEGF189、Ang2和EG-VEGFmRNA的表达与MVD正相关,rs分别为0·764、0·510、0·640和0·366,P值分别为0·000、0·000、0·000和0·003。结论:VEGF、Ang2和EG-VEGFmRNA与肝癌发生和MVD相关,并通过调控血管生成,促进肝癌门静脉瘤栓的形成。

OBJECTIVE.. To study the correlation between the expressions of vascular endothelial growth factor （VEGF）, angiopoietin 2 （Ang2）, ephrinB2 and endocrine gland-derived vascular endothelial growth factor （EG-VEGF） with carcionogenesis or portal vein tumor thrombus （PVTT） formation in human hepatocellular carcinoma （HCC）. METHODS： Expressions of VEGF, Ang2, ephrinB2 and EG-VEGF were detected by RT-PCR in 54 cases of HCC without PVTT （group A）, 9 cases of HCC with PVTT （group B）, and 10 cirrhosis tissues （group C） 10 normal liver tissues （group D）. The samples were also stained with CD34 by immunohistochemistry. Quantitation of microvessel density （MVD） and semi-quantitation of VEGF, Ang2, ephrinB2 and EG-VEGF expressions were analyzed to find the relations. RESULTS： The MVD（s） were 146. 69±77. 79, 214.07±54.41, 32.85±8. 49 and 34.83± 8. 29 in group A-D respectively with significant difference （F= 19. 77,P=0. 000）. The MVD in group A was higher than that in group C （P=0. 006）, but lower than that in group B （P= 0. 000）. The expression levels of VEGF165, VEGF189, Ang2 and EG-VEGF mRNA were significantly different among the groups. The expression levels of VEGF165, Ang2 and EG-VEGF mRNA in group A were all higher than those in group C, but lower than those in group B （P〈0. 05 or 0. 01）. The MVD was significantly correlated with VEGF165, VEGF189, Ang2 and EG-VEGF mRNA with Spearman＇s related coefficient being 0. 764, 0. 510, 0. 640 and 0. 366 respectively in HCC （P=0. 000, 0. 000, 0. 000 and 0. 003）. CONCLUSIONS：VEGF, Ang2 and EG-VEGF mRNA may play sowe roles in angiogenesis and carcinogenesis of HCC. They can promote PVTT formation in HCC by modulating angiogenesis.