EphA8在结肠癌组织中的表达和临床意义

Expression and clinical significance of EphA8 in colon cancer

目的探讨EphA8在结肠癌组织中的表达情况和临床意义。方法采用实时定量RT．PCR和Westernblot检测EphA8mRNA和蛋白在1种正常结肠黏膜细胞株和2种结肠癌细胞株中的表达情况。采用免疫组织化学法检测98例结肠癌组织和12例正常结肠组织中EphA8和血管内皮生长因子（VEGF）的蛋白表达情况，同时使用CD31染色检测肿瘤微血管密度（MVD）情况，并分析EphA8与VEGF和MVD的关系及其与病理分期、预后的关系。结果EphA8的mRNA在结肠癌细胞株的表达明显高于正常结肠黏膜细胞株（t=11．98，13．54，均P〈0．001）。EphA8蛋白在结肠癌细胞株的表达也明显高于正常结肠黏膜细胞株（t=4．63，P=0．006；t=4．92，P=0．004）。免疫组织化学结果表明EphA8蛋白在结肠癌组织高表达，且癌组织中EphA8的蛋白表达与肿瘤大小（X^2=22．97，P〈0．001）、分期（P〈0．001）、分化程度（P=0．007）、淋巴结转移（P〈0．001）、远处转移（X^2=6．97，P=0．008）以及患者生存率（X^2=17．3，P〈0．001）存在显著相关性，而与患者的性别和年龄没有明显相关性（X^2=1．36，P=0．30；X^2=0．83，P=0．44）。此外，EphA8与VEGF和MVD的表达呈正相关（r=0．434，P〈0．001；r=O．584，P〈0．001）。结论EphA8在结肠癌的恶性发展和转移中有重要作用，因此，EphA8对于结肠癌的治疗干预和预后判断具有潜在的临床应用价值。

Objective To investigate the expression of EphA8 in colon cancer and its clinical significance. Methods Real-time quantitative polymerase chain reaction （RT-PCR） and Western blot were respectively used to assess the expressions of EphA8 mRNA and protein in normal colon mucosa cell line and colon cancer cell lines. Im- munohistochemistry for EphA8 and vascular endothelial growth factor （VEGF） were performed in 98 cases of colon cancer and 12 matched normal mueosa tissues. CD31 immunohistochemical staining was used for mierovascular den- sity （MVD） counting. The relationships between the expression of EphA8 and the expression of VEGF and MVD, the clinical pathological significance, and the prognosis of patients were analyzed by statistical methods. Results EphA8 mRNA expressions were significantly higher in colon cancer cell lines than those in normal mucosa cell line （t = 11.98,13.54, P 〈0. 001 ）. EphA8 protein expressions were significantly higher in colon cancer cell lines than those in normal mueosa cell line （ t = 4.63, P = 0.006; t = 4. 92, P =0. 004）. The high expression of EphA8 was closely related to tumor size （X^2= 22.97, P 〈0. 1301 ）, TNM stage （P 〈 0.1301 ）, differentiated degree （ P = 0. 007 ） and lymph node metastasis （P 〈 0.001 ）, distant metastasis （X^2 = 6.97, P = 0. 008 ） and poor survival rate （ X^2 = 17.3, P〈0.001）. But it was not associated with the gender and age （X^2 =1.36, P=0.30; X^2 =0.83, P =0.44）. Besides, EphA8 had positive correlation with the VEGF and MVD （ r = 0. 434, P 〈 0. 001 ; r = 0. 584, P 〈 0.001 ）. Conclusion EphA8 may play important roles in the development and metastasis of colon cancer, which has poten- tial clinical values in the therapeutic intervention and prognosis of colon cancer.