廖茂良+叶银燕+熊娅琳

[摘要] 目的 探讨切除修复交叉互补基因 1（ERCC1） 和核苷酸还原酶M1亚基（RRM1） 表达与Ⅱ～Ⅳ期非小细胞肺癌（NSCLC）术后吉西他滨联合顺铂（GP方案）辅助化疗预后的关系。方法 实时荧光定量PCR法检测ERCC1、RRM1表达，Cox回归分析筛选影响预后的独立危险因子，Kaplan -Meier生存曲线分析比较各组患者的中位生存时间。结果 TNM分期、术后辅助化疗与否、手术彻底程度为影响术后生存时间的独立危险因子。 ERCC1或RRM1低表达组中化疗患者中位生存期显著优于未化疗患者（P 均<0.01）。结论 ERCC1或RRM1低表达的NSCLC患者更能从GP方案化疗中受益。

[关键词] 非小细胞肺癌；吉西他滨/顺铂；ERCC1；RRM1

[中图分类号] R734.2 [文献标识码] B [文章编号] 1673-9701（2014）17-0137-04

Effects of expression of ERCC1， RRM1 on survival trend of stage Ⅱ～Ⅳ non small cell lung cancer with gemcitabine combine cisplatin chemotherapy after surgical resection

LIAO Maoliang YE Yinyan XIONG Yalin

Department of Clinical Laboratory， Cixi Union Hospital in Zhejiang Province，Cixi 315301， China

[Abstract] Objective To investigate the effects of expression of excision repair cross complementing gene 1 （ERCC1）， ribonucleotide reductase subunit M1（RRM1） on prognosis of stage Ⅱ～Ⅳ non small cell lung cancer with gemcitabine combine cisplatin chemotherapy after Surgical Resection. Methods Real-time PCR was performed to investigate ERCC1， RRM1 expression. Cox proportional regression analysis was used to screen independent prognostic risk factors for survival. The median survival time among groups were compared by Kaplan-Meier analysis. Results TNM stage， chemotherapy after surgical resection andthe extent of tumor resection were independent prognostic factors. In the group with low expression of ERCC1 or RRM1， the median survival time of patients who had received postoperative chemotherapy was significantly improved （P<0.01）. Conclusion The NSCLC patients with low expression of ERCC1 or low expression of RRM1 get more probablely benefits from postoperative gemcitabine combine cisplatin chemotherapy.

[Key words] Non small cell lung cancer； Gemcitabine/cisplatin； ERCC1； RRM1

绝大部分肺癌获得诊断时均已到临床Ⅱ期及以上，诊断时单纯手术根治的机会亦较小，术后通常需要辅助化疗来改善预后[1]。近年来，多项国际临床研究已初步证实辅助化疗能改善术后非小细胞肺癌 （non small cell lung cancer，NSCLC） 患者的生存[1-3]。然而，目前研究的辅助化疗方案仅能使近25%～30%的患者在长期生存中获益[4-6]。因此，如何选择最佳化疗方案、以实现个体化治疗策略、提高辅助化疗疗效，成为研究的新课题。研究表明[7-9]，切除修复交叉互补基因1（ERCC1）是与铂类耐药性相关的分子预测标记、核苷酸还原酶M1亚基（RRM1）与吉西他滨（gemcitabine，GEMZ） 耐药相关的分子标记物。目前普遍认为，ERCC1、RRM1基因均与细胞内核苷酸切除修复系统的DNA损伤修复有关，因此也被认为可能与化疗个体化差异有关。目前临床中常用的辅助化疗方案中，吉西他滨联合顺铂（GP）方案为标准化治疗方案之一。为明确常见分子标记物对NSCLC术后常用辅助化疗方案疗效的预测价值，本文拟探讨Ⅱ期及Ⅱ期以上癌组织中ERCC1、RRM1表达水平与术后接受GP方案辅助化疗疗效及预后的关系。……