ERCC1、DNA-PKcs蛋白在非小细胞肺癌中的表达与预后的关系

The expression of ERCC1,DNA-PKcs protein and the relation to prognosis in non-small cell lung cancer

背景与目的已有的研究结果显示:ERCC1、DNA-PKcs是重要的DNA损伤修复因子,在肿瘤发生及预后中起着重要作用,本研究的目的是探讨DNA修复因子ERCC1,DNA-PKcs蛋白在非小细胞肺癌中表达的临床意义及其与NSCLC预后的关系。方法收集116例非小细胞肺癌组织及12例癌旁正常肺组织石蜡标本制成组织芯片,利用免疫组化SP法检测ERCC1、DNA-PKcs的表达,并分析其与临床各因素的关系。结果116例NSCLC组织中ERCC1、DNA-PKcs蛋白的阳性表达率分别为40.5%(47/116)、75%(87/116),ERCC1在肺癌组织和癌旁正常肺组织中的表达无统计学差异(P>0.05),而DNA-PKcs在癌组织中表达高于癌旁组织(P=0.000)。ERCC1的表达与肺癌分化程度、肿瘤大小和TNM分期密切相关(P<0.05),ERCC1阳性表达组5年生存率(53.2%)高于阴性表达组(26.1%)(P=0.014),但ERCC1表达不是独立的预后因素。DNA-PKcs表达与临床病理特征及预后无关。结论ERCC1阳性者预后较好,提示其表达对预后评估有一定的指导价值。

Backgroud and Objective The results of many studies have proven that excision repair crosscomplementation group 1 （ERCC1） and DNA-dependent protein kinase catalytic subunit（DNA-PKcs）,as the key genes in the repairment of DNA damage, are related to carcinogenesis and tumor progression. The aim of this study is to investigate the expression and clinical significance of ERCC1 and DNA-PKcs in patients with NSCLC,and analyze the relationship between their expression and the prognosis. Methods Paraffin-embedded operative specimens from 116 patients with non-small cell lung cancer and 12 normal lung tissues adjacent to the cancer tissues were collected, with which tissue microarray was constructed. The expression of ERCC1 and DNA-PKcs protein were detected with immunohistochemsitry. Results The positive rate of ERCC1 and DNA-PKcs expression in NSCLC was 40.5% and 75% ,respectively.There were no significant difference between ERCC1 expresson in cancer tissue and normal tissue （P=0.106）.The expression of DNA-PKcs in NSCLC was significantly higher than that in normal lung tissue adjacent to the cancer tissues（ X^ 2=17.467, P=0.000）. The expression of ERCC1 was closely related to differentiation of the cancer（X^2=5.160, P=0.023）, tumor size（X^2=7.068, P=0.008） and TNM stage（X^2=4.033, P=0.045）, but not to age and sex of the patients, smoke, lymph node metastasis, tumors histological type. The results showed that the patients with high expression of ERCC1 seemed to have better prognosis. The five-year survival rate of NSCLC patients with ERCC1 positive expression were higher than those with ERCC1 negative expression（P=0.014）.The expression of DNA-PKcs was not related to all clinical characteristics and prognosis of NSCLC patients（P〉0.05）. Multivariate analysis showed that TNM stage rather than ERCC1 and DNA-PKcs was the independent predictor for the prognosis for survival （P=0.000）. Conclusion The expression of ERCC1 may be associated with better survival, which may be useful to predict prognosis of NSCLC patients.