机构地区:[1]解放军第117医院呼吸内科,杭州310004 [2]浙江中医药大学第二临床学院
出 处:《中华肿瘤杂志》2012年第6期436-440,共5页Chinese Journal of Oncology
基 金:基金项目:浙江省医药卫生科学研究基金(2008A0144)
摘 要:目的探讨非小细胞肺癌(NSCLC)组织和不同转移潜能肺癌细胞系中埃兹蛋白(ezrin)的表达,以及NSCLC组织中ezrin与E-钙黏蛋白(E—cadherin)和CD44V6蛋白表达之间的关系。方法采用半定量逆转录聚合酶链反应(RT-PCR)和Westernblot法,检测不同肺癌细胞系中ezrinmRNA和蛋白的表达水平。采用免疫组织化学SP法,检测150例NSCLC组织中ezrin、E-cadherin和CD44V6蛋白的表达,并联合应用Westernblot法对30例新鲜NSCLC组织及相应癌旁正常组织中ezrin蛋白的表达进行分析。结果高转移性肺癌细胞系中ezrinmRNA和蛋白的表达明显高于低转移性肺癌细胞系。150例NSCLC组织中,ezrin、E—cadherin和CD44V6蛋白的阳性表达率分别为61.3%、54.0%和58.7%。ezrin蛋白的表达与NSCLC患者的性别、年龄、肿瘤大小、组织类型、临床分期以及病理分级均无关(均P〉0.05),仅与淋巴结转移情况有关(r=9.013,P〈0.01)。Westernblot检测结果显示,ezrin蛋白在30例新鲜NSCLC组织中的相对表达量为1.12±0.41,明显高于相应的癌旁正常组织(0.61±0.28,P〈0.01)。ezrin蛋白阴性表达患者的5年生存率为29.3%,明显高于ezrin蛋白阳性表达患者(15.2%,P=0.042)。Cox多因素分析的结果显示,淋巴结转移和ezrin蛋白的表达是影响NSCLC患者预后的危险因素(均P〈0.05)。ezrin蛋白在NSCLC组织中的表达与E-cadherin蛋白的表达呈负相关,与CD44V6蛋白的表达呈正相关(均P〈0.05)。结论ezrin、E-eadherin和CD44V6在NSCLC的生长和转移过程中发挥着重要的调控作用,联合检测ezrin、E-eadherin和CD44V6蛋白的表达可作为判断NSCLC转移和预后的重要生物学指标。Objective To explore the expression of ezrin protein in human non-small cell lung cancer (NSCLC) tissues and lung cancer cell lines, and the association between the expression of ezrin protein and the expression of E-cadherin and CD44V6 proteins. Methods The expression of ezrin protein and mRNA in lung cancer cell lines was detected by RT-PCR and Western blotting. Ezrin, E-cadherin and CD44V6 were detected by immunohistochemical SP staining in tumor tissues from 150 lung cancer cases and in adjacent normal lung tissues from 30 patients. Furthermore, the expression of ezrin in 30 freshly-taken NSCLC tissues was also detected by Western blot. Results The expression of ezrin protein and mRNA was up-regulated in highly metastatic human lung cancer. The positive rate of ezrin, E-cadherin and CD44V6 expression in the lung cancer was 61.3% , 54.0% and 58.7% , respectively. The up-regulation of ezrin expression was significantly correlated with lymph node metastasis, but not correlated with age, sex, tumor size,histological type, clinical TNM system and pathological grade. Western blot analysis showed that the level of ezrin in the NSCLC tissues was significantly higher than that in the normal tissues (t =5. 013, P 〈 0.01 ). Survival analysis showed that the 5-year survival rate of patients with negative ezrin expression was 29.3%, significantly higher than that of patients with positive ezrin expression ( 15.2%, x2 =4. 128 ,P =0.042). Multivariate Cox regression analysis showed that ezrin expression ( RR = 3. 012, P = 0. 047) and lymph node metastasis ( RR = 4. 827, P = 0. 035 ) were significantly independent prognostic factors for patients with lung cancer. Furthermore, a negative correlation was observed between the expressions of ezrin and E-cadherin in lung cancer, and a positive correlation between the expressions of ezrin and CD44V6 in lung cancer. Conclusions Ezrin, E-cadherin and CD44V6 play an important role in the regulation of growth and meastasis of lung cancer. Combined detection of ez
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