非小细胞肺癌组织中 ERCC1 mRNA、蛋白的表达变化及意义

摘要

目的：观察非小细胞肺癌（NSCLC）肿瘤组织中切除修复交叉互补组l（ERCC1）的基因和蛋白表达变化，并探讨其意义。方法212例NSCLC患者，根治性手术且术后辅助铂类化疗，采用实时荧光定量逆转录聚合酶链反应（ RT-PCR）和免疫组化法分别检测手术切除肿瘤组织中ERCC1 mRNA和蛋白的表达，并分析其和患者预后生存的关系。结果212例患者中79例（37．26％）患者ERCC1 mRNA低表达，133例（62．74％）高表达；70例（33．02％）患者ERCC1蛋白低表达，142例（66．98％）高表达。 ERCC1 mRNA表达水平与临床分期（P＜0．0001）、病理类型（P＝0．005）、分化程度（P＝0．028）、淋巴转移（P＜0．0001）有关；ERCC1蛋白表达水平与临床分期（P＝0．015）、病理类型（P＝0．016）、淋巴结转移（P＝0．018）有关。 NSCLC患者ERCC1 mRNA低表达者的中位无疾病生存时间（DFS）明显长于高表达者（25．9νs 19．4个月，P＜0．0001）。但NSCLC患者的ERCC1蛋白低表达者的中位DFS与高表达者比较无明显差异（21．5νs 21．0个月，P＝0．282）。多因素回归分析结果显示只有临床分期是影响患者DFS的独立预后因素。 ERCC1 mRNA水平与ERCC1蛋白表达之间呈负相关（r＝-0．230，P＝0．001）。结论行手术切除且术后行铂类辅助化疗的NSCLC患者中，ERCC1 mRNA低表达者比高表达者的DFS延长，且可以从铂类化疗中获益，ERCC1 mRNA的表达水平比ERCC1蛋白表达水平更适合作为以铂类为基础化疗NSCLC患者预后和预测指标。%Objective To detect the mRNA and protein expression of ERCC 1 in human non-small cell lung carcinoma (NSCLC), and the correlation between them,and to investigate its relationship with prognosis following post-operative adju-vant platinum chemotherapy .Methods:The expression of ERCC 1 protein was examined by immunohistochemistry ( IHC) , and the expression of ERCC1 mRNA was examined by RT-PCR.we had analyzed 212 patients with NSCLC who underwent post-operative adjuvant platinum chemotherapy .The relationship of ERCC1 with disease-free survival ( DFS) and overall survival (OS) was analyzed.Results: ERCC1 with mRNA low expression patients disease free survival was significantly prolonged compared with High expression patients (median DFS 25.9 vs 15.4 months, P <0.0001).Multivariate Cox re-gression analysis showed that clinical TNM stage (HR=2.936, P=0.022) were significant independent predictors of DFS for patients with lung cancer , but There was no significant difference between the DFS of low ERCC 1 protein expression and high ERCC1 protein expression(median DFS 21.5 νs 21.0 months,P =0.282).Multivariate Cox regression analysis showed that clinical TNM stage(HR=2.726, P=0.033)were significant independent predictors of DFS for patients with lung cancer.the expression of ERCC1 mRNA was negatively related to the expression of ERCC 1 protein.Conclusion: the patients of stage Ⅰ-ⅢA with low expression of ERCC 1 had a longer disease-free survival than those with high expression of ERCCl.ERCC1 mRNA low expression was in relation with better prognosis following Adjuvant Cisplatin Chemotherapy in Operable NSCLC .The expression of ERCC1 mRNA was more suitable than the expression of ERCC 1 protein as a prognos-tic factor and predictive marker for platinum-based chemotherapy in operable NSCLC .