凋亡抑制基因Survivin在非小细胞肺癌中的表达及其与Bcl-2、Bax蛋白表达的关系

目的　探讨Survivin基因的表达在肺癌发生、发展中的作用及其与Bax、Bcl 2蛋白表达的相互关系。方法　对 12例正常支气管粘膜上皮、9例不典型增生、3 4例肺癌及 12例淋巴结转移癌石蜡切片组织 ,应用原位分子杂交法检测SurvivinmRNA的表达 ;用免疫组织化学链霉菌抗生物素蛋白 过氧化酶法 (S P法 )检测Bcl 2、Bax蛋白的表达。结果　肺癌、淋巴结转移癌中SurvivinmRNA阳性率分别为 61.76%及 91.67% ,显著高于正常支气管粘膜上皮及不典型增生中的阳性率16.7%及 3 3 .3 % (P均 <0 .0 5 ) ;低分化、中分化肺癌中阳性率 88.89%、75 .0 0 %较高分化 11.11%明显升高 (P均 <0 .0 1)。TNM分期Ⅲ期病例中SurvivinmRNA表达阳性率 93 .3 %高于Ⅰ Ⅱ期病例的 3 6.8% (P <0 .0 1)。SurvivinmRNA表达与Bcl 2蛋白表达呈正相关 (P <0 .0 1)结论　Sur vivin基因在非小细胞肺癌中表达上调 ,提示其通过抑制细胞凋亡 ,在肺癌癌变发生、发展中起重要作用 ,可能成为肺癌基因治疗的新靶点 ,其阳性表达亦预示肿瘤有较高的侵袭性和不良预后 ,Sur vivin基因与凋亡抑制基因Bcl 2的共同表达可能在肺癌中起协同作用。

Expression of Survivin in human non-small-cell lung cancer and its association with Bcl-2 and Bax

Objective To investigate the expression of Survivin and its relationship with expression of B-cell lymphoma-2 (Bcl-2),Bax in human non-small-cell lung carcinoma (NSCLC).Methods The expression of the survivin mRNA was detected by in situ hybridization (ISH) in 12 cases of normal bronchial epithelium,9 cases of dysplasia,34 cases of NSCLC and 12 cases of lymph node metastasis.Immunohistochemical assay was used to detect the expression of Bcl-2 and Bax proteins.Results The positive expression rate of Survivin in NSCLC (61.76%) and lymph node metastasis (91.67%) was significantly higher than in normal bronchial epithelium (16.7%) and dysplasia (33.3%, P <0.05).The up-regulation of the expression of Survivin was related to the TNM stages ( P <0.01) and differentiation ( P < 0.05).The expression of Bcl-2 was positively correlated with the expression of surviving ( P < 0.01). Conclusion Survivin gene may play an important role in the pathway of carcinogenesis and progression of NSCLC and it may be identified as a new therapeutic target.The up-regulation of the expression of Survivin predicts more invasion and poor prognosis.Survivin and Bcl-2 might play synergetic roles in NSCLC.