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人脑星形细胞瘤中EphA2-ephrinA1、CD105的表达及与预后的关系

Expressions of EphA2-ephrinA1 and CD105 in Human Astrocytoma and Their Relationship with Prognosis

  • 摘要: 目的 检测酪氨酸激酶受体EphA2及配体ephrinA1在人脑星形细胞瘤中的表达,并探讨其与脑星形细胞瘤预后的关系。方法 采用免疫组织化学法检测55例手术切除人脑星形细胞瘤组织及15 例正常脑组织中EphA2、ephrinA1的表达情况,并采用CD105抗体标记微血管内皮细胞,计算微血管密度(MVD)。结果 EphA2(51/55)、CD105-MVD(34.26±12.61)在星形细胞瘤中阳性表达明显高于正常脑组织,两者差异有统计学意义(P<0.01);而且随着星形细胞瘤病理级别越高,EphA2及CD105-MVD蛋白染色强度和阳性细胞数均明显升高,ephrinA1则具有相反的趋势,随星形细胞瘤级别越低ephrinA1表达越高。EphA2表达与CD105-MVD呈显著正相关( r=0.713, P<0.05),ephrinA1表达与CD105-MVD呈显著负相关( r=-0. 772, P < 0. 05),EphA2的表达与ephrinA1的表达呈显著负相关( r=-0. 912, P < 0. 05)。EphA2、CD105-MVD和ephrinA1均是重要的星形细胞瘤预后相关风险因子。EphA2、CD105-MVD阳性ephrinA1阴性的星形细胞瘤患者较三者均阳性或三者均阴性或EphA2、CD105-MVD阴性ephrinA1阳性的患者生存期明显缩短。结论 EphA2及CD105-MVD在星形细胞瘤中特异性高表达、ephrinA1特异性低表达与星形细胞瘤不良预后密切相关,EphA2和ephrinA1有望成为脑星形细胞瘤诊断和特异性靶向治疗及预后评估的新靶点。

     

    Abstract: Objective To investigate the expressions of tyrosine kinase receptor EphA2 and ligand ephrinA1 in human astrocytoma and their correlations with prognosis. Methods Expression levels of EphA2 and ephrinA1 were detected by immunohistochemical assay in 55 cases of surgically resected human astrocytoma tissues and 15 cases of normal brain tissues. CD105-stained microvessel density (MVD) in microvascular endothelial cells were also measured. Results Expressions of EphA2(51/55) and CD105-MVD (34.26±12.61) in human astrocytomas were signifi cantly higher than those in normal brain tissues(P<0.01). With the increased pathology grade of human astrocytomas, ephrinA1 expression was decreased; CD105-MVD was significantly positively correlated with EphA2 expression (r=0.713, P<0.01), and significantly negatively correlated with ephrinA1 expression (r=-0. 772, P<0.01). EphA2 was signifi cantly negatively correlated with ephrinA1 expression (r=-0.912, P<0.01). EphA2, CD105-MVD and ephrinA1 were all important risk factors for astrocytomas prognosis. Overall and progression-free survival of patients with positive EphA2 and CD105-MVD and negative ephrinA1 was signifi cantly shorter than those with all positive EphA2, CD105-MVD and ephrinA1, all negative EphA2, CD105-MVD and ephrinA1, or negative EphA2 and CD105-MVD and positive ephrinA1. Conclusion EphA2 and CD105-MVD are specifically up-regulated and ligand ephrinA1 is specifi cally down-regulated in astrocytomas and may be closely involved in the poor prognosis. EphA2 and ephrinA1 could be the new targets for diagnosis, therapeutic and prognosis evaluation of human brain astrocytomas.

     

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