Pygopus2过表达与非小细胞肺癌恶性程度的关系

Relationship between abnormal expression of Pygopus2 and malignant phenotype in non-small cell lung cancer patients

目的 Pygopus2(Pygo2)是经典Wnt/β-catenin信号通路的重要成员,本研究探讨Pygo 2的表达与非小细胞肺癌恶性程度的关系。方法选择168例原发性肺鳞癌、腺癌标本,应用SP免疫组化染色及Western Blot方法,检测肺癌组织中Pygo2蛋白的表达情况及其与临床病理因素的关系;体外培养人正常支气管上皮细胞系HBE、人肺癌细胞系,RT-PCR检测各细胞系Pygo2 mRNA表达。结果免疫组化染色结果显示:在正常支气管上皮细胞的胞核中Pygo2蛋白几乎不表达,而在非小细胞肺癌胞核中存在Pygo2蛋白的异常表达,表达率为68.45%。分期晚、分化差的癌组织更易出现Pygo2蛋白过表达(P均<0.05)。Pygo2蛋白过表达患者的平均生存时间和5年生存率明显低于Pygo2正常表达的患者(P均<0.05)。Western Blot结果显示,在癌旁正常肺组织可见Pygo2蛋白的弱表达,而在肺癌组织中Pygo2蛋白的表达明显高于正常肺组织(P<0.01)。RT-PCR检测细胞系Pygo2 mRNA发现,与正常支气管上皮细胞系HBE相比,肺癌细胞系中均显示出Pygo2 mRNA不同程度的表达增强(P均<0.05)。结论 Pygo2的过表达可能与非小细胞肺癌的恶性程度有关。

Objective To investigate the relationship between expression of Pygopus2（ Pygo2）,an important member of the classical Wnt/beta-catenin signal pathway and the malignant degree of non-small cell lung cancer（ NSCLC）. Methods One hundred and sixty eighty primary lung squamous cell carcinoma or adenocarcinoma tissues samples were selected. SP immunohistochemical staining and Western Blot methods were used to detect the expression of Pygo2 protein in lung cancer tissues and analyze the relationship between Pygo2 protein expression and clinicopathological characteristics. Human normal bronchial epithelial cell line HBE and human lung cancer cell lines were cultured in vitro,and RT-PCR method was used to detect the expression of Pygo2 mRNA in different cell lines. Results Immunochemistry result showed that there was almost no expression of Pygo2 protein in the nucleus of normal bronchial epithelial cells,while there was abnormal expression of Pygo2 protein in the nucleus of NSCLC cells with 68. 45% abnormal expression rate. The Pygo2 protein over-expression was significantly associated with late stage of TNM,poor differentiation of cancer tissues（ all P 0. 05）. The mean survival time and 5-year survival rate in patients with Pygo2 protein over-expression were significantly lower than those in patients with Pygo2 protein normal expression（ all P 0. 05）. Western Blot method showed that there was weak expression of Pygo2 protein in normal lung tissues adjacent to cancer,while Pygo2 protein expression in lung cancer tissues was significantly higher than that in normal lung tissues adjacent to cancer（ P 0. 01）. RT-PCR showed that Pygo2 mRNA expressions in human lung cancer cell lines were significantly higher than that in human normal bronchial epithelial cell line HBE（ all P 0. 05）. Conclusion Pygo2 over-expression may be associated with the extent of malignancy of NSCLC.