Cyclin A、CDK2基因在非小细胞肺癌中的表达及其意义

Significance of Cyclin ACDK2 Expression in Non-Small-Cell Lung Cancer

目的研究细胞周期素A(CyclinA)和细胞周期素依赖性激酶2(cyclin-dependentkinases,CDK2)基因在非小细胞肺癌(non-small-celllungcancer,NSCLC)组织中的表达及其相互关系,探讨其对NSCLC发生、发展、淋巴结转移及预后的影响。方法采用免疫组织化学二步法检测40例NSCLC(伴淋巴结转移21例,不伴淋巴结转移19例),11例支气管黏膜上皮增生或不典型增生,9例淋巴结转移癌组织中CyclinA、CDK2蛋白的表达,并随访40例NSCLC患者3年生存期。结果在支气管黏膜上皮增生或不典型增生,不伴淋巴结转移的NSCLC,伴淋巴结转移的NSCLC,淋巴结转移癌组织中,CyclinA蛋白的阳性表达率分别为9.09%(1/11),31.58%(6/19),80.95%(17/21),66.67%(6/9);CDK2蛋白的阳性表达率分别为9.09%(1/11),36.84%(7/19),76.19%(16/21),77.78%(7/9);不伴淋巴结转移的NSCLC组织中的CyclinA、CDK2蛋白阳性表达率分别与伴淋巴结转移NSCLC组织、淋巴结转移癌组织的CyclinA、CDK2蛋白阳性表达率比较,差异均有显著性(P均<0.05)。23例CyclinA蛋白表达阳性患者3年生存率为21.74%(5/23),17例表达阴性患者3年生存率为58.82%(10/17),两者比较有显著性差异(P<0.05);23例CDK2蛋白表达阳性患者3年生存率为17.39%(4/23),17例表达阴性患者3年生存率为64.71%(11/17),两者比较有显著性差异(P<0.05)。NSCLC中CyclinA与CDK2蛋白表达呈正相关(χ2=19.22,P<0.001,列联系数Pearson=0.570)。结论在NSCLC发生、演进、浸润、淋巴结转移过程中CyclinA、CDK2起正调控作用,NSCLC组织中CyclinA、CDK2表达上调可作为判断NSCLC预后不良的参考指标。

Objective To investigate the expression and their mutual relation of the CyclinA,CDK2 gene in human nonsmall-cell lung cancer（NSCLC）, and to study their role in the carcinogenesis,development ,lymphy nodes metastases and prognosis of NSCLC. Methods The expression of cyclin A and CDK2 was tested by immunohistochemical method（two steps method） in 40 cases of NSCLC（21 cases with lymphy nodes metastases）, 11 cases of bronchial epithelium dysplasia and 9 specimens of lymph nodes metastases. The 3-years survival rate was observed in the follow-up period of 40 cases of NSCLC. Results In bronchial epithelium dysplasia, NSCLC without and with lymphy nodes metastases,and specimens of lymphy nodes metastases, the positive rate of Cyclin A protein was 9.09 % （1/11） ,31.58% （6/19） ,80.95% （17/21） and 66.67% （6/9）respectively, the positive rate of CDK2 protein was 9.09 % （ 1/11 ）, 36.84 % （7/19）, 76.19 % （ 16/21 ） and 77.78 % （7/9） respectively. The expression of Cyclin A and CDK2 was sight ficantly different between NSCLC with or without lymphy nodes metastases（P〈0.05）. The 3-year survival rate was 21,74 % （5/23） for positive Cyclin A patients and 58.82% （10/17） for negative Cyclin A patients, showing a significant difference（ P〈0.05）. The 3-year survival rate was 17.39 % （4/23） for positive CDK2 patients and 64.71% （11/17） for negative CDK2 patients,showing a significant difference（P〈0.05）. Cyclin A expression positively correlated with CDK2 expression （x^2=19.22, P〈0. 001, Pearson=0. 570）. Conclusion Cyclin A and CDK2 might play an important role in the carcinogenesis, development, and lymphy nodes metastases of NSCLC. Up-regulation of Cyclin A and CDK2 expression indicates a poor prognosis for patients with NSCLC.