α-微管蛋白和多药耐药基因1表达与肺癌生物学特性的相关性

Expression of α-tubulin and MDR1 and their correlation with the biological features of non-small cell lung carcinoma

目的探讨α-微管蛋白和多药耐药基因1（MDR1）在原发性非小细胞肺癌（NSCLC）中的表达特征及其临床意义。方法采用免疫组化sP法检测158例NSCLC组织中α-微管蛋白和MDR1的表达情况，采用Westernblot方法检测30例新鲜NSCLC组织及相应癌旁正常组织中α-微管蛋白和MDR1的表达，分析两者表达与肺癌生物学特性的关系。结果α-微管蛋白和MDR1在NSCLC中的阳性表达率分别为65．2％和51．3％，而30例癌旁组织中均未见α-微管蛋白和MDR1阳性表达。Westernblot检测结果显示，α-微管蛋白和MDR1在30例新鲜NSCLC组织中的表达（0．49±0．06和0．56±0．04）明显高于相应癌旁肺组织（0．07±0．01，0．65±0．02；t=3．693，t=6．769，P〈0．01）。α-微管蛋白在Ⅰ～Ⅱ期与Ⅲ～Ⅳ期NSCLC中的阳性表达率差异有统计学意义（P〈0．01），在中、高分化NSCLC中的阳性表达率明显低于低分化NSCLC（P〈0．01）。α-微管蛋白的表达与患者的年龄、性别、组织类型、肿瘤大小以及淋巴结转移无明显关系（P〉0．05），MDR1的表达与患者的年龄、性别、临床分期、肿瘤大小、病理分级以及淋巴结转移无关（P〉0．05）。在不同组织类型中，MDR1的表达水平有较大差异，肺腺癌中的MDR1阳性表达率明显高于鳞癌和大细胞癌（P〈0．01）。α-微管蛋白和MDR1的表达与化疗疗效无关Х^2=0．69，Х^2=1．30，P〉0．05）。单因素生存分析显示，α-微管蛋白和MDR1阴性患者的5年生存率分别为30．7％和28．5％，明显高于α-微管蛋白和MDR1阳性表达患者（13．5％和11．8％），差异有统计学意义（Х^2=20．69，Х^2=15．52，P〈0．01）。多因素生存分析显示，α-微管蛋白（RR=3．287，P=0．006）和临床分期（RR=1．954，P=0．025）可作为独立的预后指标。α-微管蛋白和MDRI在肺癌组织中的表达无明显相关性（r=0．093，P〉0．05）。结论α-微管蛋白和MDR1在肺癌的发生和恶性进展中有一定作用，联合检测可作为判断肺癌预后的重要指标。

Objective To detect the expression of α-tubulin and MDR1 in human non-small cell lung carcinoma （NSCLC）, and to clarify their clinical significance. Methods Paraffin embedded tissues from 158 primary non-small lung carcinomas and 30 paracancerous lung tissues were examined for expression of α-tubulin and MDR1 by immunohistochemistry （SP method ）. 30 freshly taken NSCLC tissues were examined by Western blot analysis. The relationship between α-tubulin and MDR1 expression and the biological features of lung carcinoma was analyzed. Results The positive rate of α-tubulin and MDR1 expressions in the lung carcinomas was 65.2% and 51.3%, respectively. There was no expression of either of them in 30 paracancerous lung tissues. Western blot analysis showed that the level of α-tubulin and MDR1 expressions in NSCLC tissues were 0.49 ± 0.06 and 0.56 ± 0.04, respectively, significantly higher than that in paracancerous tissues （0. 07 ± 0.01） （t = 3. 693 and t = 6. 769, P 〈 0.01 ）. The positive rate of α-tubulin expression was gradually increased with tumor progression, significantly higher in Ⅲ-Ⅳ stage cancers and in poorly differentiated carcinomas （both P 〈 0.01 ）. There was a distinct statistically significant difference between stage Ⅰ , stage Ⅱ and Ⅲ, and stage Ⅳ. The positive rate of α-tubulin in well- moderately differentiated carcinomas was lower than that in poorly differentiated ones. There was no significant correlation with age, sex, tumor size, histological type, clinical TNM system and lymph node metastasis. The positive rate of MDR1 was not correlated with sex, age, tumor size, pathological grading, clinical TNM stages and lymph node metastasis. But the positive rate of MDR1 in adenocarcinoma was significantly higher than that in squamous carcinoma and undifferentiated large cell carcinomas （ P 〈 0.01 ）. α-tubulin and MDR1 expression had no impact on the outcome of chemotherapy （1/2 = 0.69 and 1.30, P 〉 0.05, respectively ）. Univariate analysis showed that the 5-year survival rate of patients with negative α-tubulin and MDR1 expression was 30.7% and 28.5% , respectively, significantly higher than that of patients with positive α-tubulin and MDR1 expression （ 13.5% and 11.8% , respectively ） （Х^2 = 20.69 and 15.52, P 〈 0.01, respectively）, and multivariate Cox regression analysis showed that α-tubulin （RR = 3. 287, P = 0. 006 ） and clinical TNM stage （ RR = 1. 954, P = 0. 025 ） were significantly independent predictive factor for patients with lung cancer, MDR1 and other factors could not be used as an independent predicitive factors. However, there was no significant correlation between the expression of α-tubulin and MDR1 in lung carcinoma（r = 0. 093 ,P 〉 0.05 ）. Conclusion The expression of α-tubulin and MDR1 may play an important role in the development and progression of human non-small cell lung carcinoma. Combined detection could be considered as an important index for predicting prognosis of lung carcinoma.