肝细胞癌中Ephrin-A1及其受体的表达与血管生成的关系
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陈钢

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The relationship between the expression of Ephrin-A1 and its receptor to angiogenesis in HCC
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    摘要:

    目的:探讨Ephrin-A1 及其受体与肝细胞癌血管生成之间的关系。
    方法:采用免疫组织化学SP法和逆转录聚合酶链反应(RT-PCR)检测52例肝细胞癌(肝癌组)和癌旁组织(癌旁组)标本中Ephrin-A1及其受体EphA1和EphA2蛋白及mRNA的表达情况,并分析其与肝细胞癌的临床病理因素及微血管密度(microvessel density, MVD)之间的关系。
    结果:在52例肝癌组中 Ephrin-A1及其受体EphA1,EphA2的蛋白阳性表达率分别为59.6%(31/52),53.8%(28/52)和17.3%(9/52),而癌旁组织中的蛋白阳性表达率分别为23.1%(12/52),28.9% (15/52)以及21.2%(11/52)。Ephrin-A1及其受体EphA1在两组中的差异有统计学意义(P<0.05),而EphA2在两组间的差异无显著性(P>0.05)。Ephrin-A1及其受体EphA1mRNA在肝癌组的阳性表达率为67.3%(35/52)和73.7%(38/52),明显高于癌旁组中的阳性表达42.3%(22/52)和48.1% (25/52) (P<0.05),而EphA2mRNA在两组间的差异无显著性(P>0.05)。Ephrin-A1蛋白的高表达与患者的甲胎蛋白(AFP)水平及有无门静脉癌栓有关(P<0.05)。Spearman等级相关分析显示,在肝癌组中Ephrin-A1的表达与EphA1的表达呈正相关(r=0.671,P<0.01);而Ephrin-A1与EphA2的表达无相关性;肝癌组中Ephrin-A1的表达与MVD呈正相关(r=0.826,P<0.01)。
    结论:Ephrin-A1通过与其受体EphA1相结合,促进肝细胞癌的血管生成,从而促进肝细胞癌的生长、浸润和转移; Ephrin-A1及其受体EphA1有望成为肝癌抗血管生成治疗新的靶点。

    Abstract:

    Abstract:Objective:To study the relationship between Ephrin-A1 and its receptor with angiogenesis in hepatocellular carcinoma(HCC).
    Methods:Immunohistochemistry staining method (S P methods)and reverse transcription polymerase chain reaction (RT-PCR) were used to determine the protein and mRNA expression of Ephrin-A1 and its receptor EphA1、EphA2 in tumor tissues and their corresponding adjacent liver tissues from 52 HCC patients; then, analyse of the relationship between Ephrin-A1 and clinicopathologyfactor and microvessel density(MVD) in HCC was made.
    Results:The protein expression rate of Ephrin-A1 and EphA1, EphA2 in HCC was 59.6%(31/52), 53.8%(28/52)and 17.3%(9/52), respectively, but in the paired liver tissues adjacent to HCC the expression rate was 23.1%(12/52), and 21.2%(11/52), respectively. The protein expression rate of Ephrin-A1 and EphA1 was significantly higher than that in the paired liver tissues adjacent to HCC(P<0.05), The protein expression rate of EphA2 was not significant in HCC compared to the paired liver tissues adjacent to HCC(P>0.05). The mRNA express rate of Ephrin-A1 and EphA1 in HCC [67.3%(35/52) and 73.7%(38/52)] were prominently higher than those in the paired liver tissues adjacent to HCC [42.3%(22/52) and 48.1%(25/52)] (P<0.05), The mRNA express rate of EphA2 was no significant in HCC compare to the paired liver tissues adjacent to HCC(P>0.05). The higher expression of Ephrin-A1 was correlated with the AFP level and thrombus in the portal vein(P<0.05) in patients with HCC. Spearman′s rank correlation analysis indicatied the expression of Ephrin-A1 was correlated with EphA1(r=0.671,P<0.01), but was not correlated with EphA2 in HCC; and the expression of Ephrin-A1 was correlated with MVD in HCC(r=0.826,P<0.01).
    Conclusions:Ephrin-A1 can be combination with its receptor EphA1 but not with EphA2 in HCC, and can improve angiogenesis of HCC, then enhanced its growth, invasiveness and metastasis. Ephrin-A1 and EphA1 can become the new targets for the antiangiogenesis treatment of HCC.

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陈钢 , 王怡 , 易继林 , 沈文状 , 李兴睿 , 刘谨文 .肝细胞癌中Ephrin-A1及其受体的表达与血管生成的关系[J].中国普通外科杂志,2007,16(8):15-.
DOI:10.7659/j. issn.1005-6947.2007.08.015

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  • 在线发布日期: 2007-08-25