非小细胞肺癌组织中ERCC1和RRM1表达与吉西他滨/顺铂疗效及预后的关系

Correlation of expression of ERCC1/RRM1 with cisplatin combined with gemcitabine chemotherapy sensitivity and prognosis in non-small cell lung cancer

目的探讨核苷酸切除修复交错互补基因-1(ERCC1)和核糖核苷酸还原酶亚单位M1(RRM1)在非小细胞肺癌组织中的表达水平,分析其与吉西他滨/顺铂化疗敏感性及生存时间的关系。方法以71例ⅢB～Ⅳ期肺癌患者的穿刺或手术标本为材料,采用免疫组织化学方法检测其ERCC1和RRM1的表达水平。Cox回归分析筛选影响预后的独立危险因子,Kaplan-Meier生存曲线分析比较不同ERCC1和RRM1表达水平患者的中位生存期和无病进展时间。结果非小细胞肺癌组织中ERCC1的阳性率为46.5%,RRM1的阳性率为56.3%。ERCC1低表达者接受吉西他滨/顺铂的化疗效果优于高表达者,两者间的差异有统计学意义(P=0.036);RRM1低表达者接受吉西他滨/顺铂的化疗效果优于高表达者,两者间的差异具有统计学意义(P=0.003),ERCC1和RRM1低表达的患者生存期明显长于高表达者(P值分别为0.002和0.001)。结论 ERCC1和RRM1的表达可作为非小细胞肺癌患者吉西他滨/顺铂方案化疗敏感性及其预后判断的指标之一。

Objective To investigate the expression of excision repair cross-complementing gene-1（ERCC1）and ribonucleotide reductase subunit M1（RRM1）in non-small cell lung cancer（NSCLC）,and explore the correlation of ERCC1 and RRM1 expression with the therapeutical effect of cisplatin combined with gemcitabine chemotherapy and survival time in patients with NSCLC.Methods Seventy-one patients with stage-ⅢB and Ⅳ NSCLC were enrolled in the study.Immunohistochemistry for paraffin-embedded tumor specimens was performed to investigate ERCC1 and RRM1 expression.Cox regression analysis was used to screen independent risk factors for survival.Kaplan-Meier survival curve analysis was used to compare median overall survival time and median progression-free survival time among the patients of with different expression of ERCC1 and RRM1.Results The positive rates of ERCC1 and RRM1 expression in NSCLC samples were 46.5% and 56.3% respectively.The therapeutic effect of gemcitabine combined with cisplatin in patient with ERCC1 low expression was obviously better than that with ERCC1 high expression（P=0.036）.The therapeutic effect of gemcitabine/cisplatin in patients with RRM1 low expression was obviously better than that with RRM1 high expression（P=0.003）.The median overall survival time and progression-free survival time of patients with ERCC1/RRM1 low expression were obviously longer than those with high expression（P=0.002 and 0.001）.Conclusion The ERCC1 and RRM1 expression might be considered one of the predicting markers of drug sensitivity of gemcitabine/cisplatin and prognosis in NSCLC.