Chen Qing-yong, Jiang Zhong-yong, Wu Li-jun, Zhang Bao-yan, Lu Guo-hua, Zhou Jian-ying
Department of Respiratory Diseases, The 117th Hospital of PLA, Hangzhou 310013, China.
Zhonghua Zhong Liu Za Zhi. 2010 Apr;32(4):278-82.
To detect the expression of alpha-tubulin and MDR1 in human non-small cell lung carcinoma (NSCLC), and to clarify their clinical significance.
Paraffin embedded tissues from 158 primary non-small lung carcinomas and 30 paracancerous lung tissues were examined for expression of alpha-tubulin and MDR1 by immunohistochemistry (SP method). 30 freshly taken NSCLC tissues were examined by Western blot analysis. The relationship between alpha-tubulin and MDR1 expression and the biological features of lung carcinoma was analyzed.
The positive rate of alpha-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 alpha-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 alpha-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 alpha-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). alpha-tubulin and MDR1 expression had no impact on the outcome of chemotherapy (chi(2) = 0.69 and 1.30, P > 0.05, respectively). Univariate analysis showed that the 5-year survival rate of patients with negative alpha-tubulin and MDR1 expression was 30.7% and 28.5%, respectively, significantly higher than that of patients with positive alpha-tubulin and MDR1 expression (13.5% and 11.8%, respectively) (chi(2) = 20.69 and 15.52, P < 0.01, respectively), and multivariate Cox regression analysis showed that alpha-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 alpha-tubulin and MDR1 in lung carcinoma(r = 0.093, P > 0.05).
The expression of alpha-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.
检测α-微管蛋白和多药耐药基因1（MDR1）在人非小细胞肺癌（NSCLC）中的表达，阐明其临床意义。
采用免疫组织化学（SP法）检测158例原发性非小细胞肺癌组织及30例癌旁肺组织石蜡包埋标本中α-微管蛋白和MDR1的表达。采用蛋白质印迹法检测30例新鲜NSCLC组织中α-微管蛋白和MDR1的表达。分析α-微管蛋白和MDR1表达与肺癌生物学特性的关系。
肺癌组织中α-微管蛋白和MDR1的阳性表达率分别为65.2%和51.3%。30例癌旁肺组织中二者均无表达。蛋白质印迹法显示，NSCLC组织中α-微管蛋白和MDR1的表达水平分别为0.49±0.06和0.56±0.04，显著高于癌旁组织（0.07±0.01）（t=3.693，t=6.769，P<0.01）。α-微管蛋白的阳性表达率随肿瘤进展逐渐升高，在Ⅲ-Ⅳ期癌及低分化癌中显著升高（均P<0.01）。Ⅰ、Ⅱ期与Ⅲ、Ⅳ期之间差异有统计学意义。高-中分化癌中α-微管蛋白的阳性表达率低于低分化癌。其与年龄、性别、肿瘤大小、组织学类型、临床TNM分期及淋巴结转移均无显著相关性。MDR1的阳性率与性别、年龄、肿瘤大小、病理分级、临床TNM分期及淋巴结转移均无相关性。但腺癌中MDR1的阳性率显著高于鳞癌及未分化大细胞癌（P<0.01）。α-微管蛋白和MDR1的表达对化疗疗效无影响（χ2=0.69和1.30，P>0.05）。单因素分析显示，α-微管蛋白和MDR1表达阴性患者的5年生存率分别为30.7%和28.5%，显著高于α-微管蛋白和MDR1表达阳性患者（分别为13.5%和11.8%）（χ2=20.69和15.52，P<0.01），多因素Cox回归分析显示，α-微管蛋白（RR=3.287，P=0.006）和临床TNM分期（RR=1.954，P=0.025）是肺癌患者显著的独立预测因素，MDR1等因素不能作为独立预测因素。然而，肺癌中α-微管蛋白和MDR1的表达无显著相关性（r=0.093，P>0.05）。
α-微管蛋白和MDR1的表达可能在人非小细胞肺癌的发生发展中起重要作用。联合检测可作为预测肺癌预后的重要指标。
