RRM1和ERCC1基因外周血中表达水平与吉西他滨联合铂类治疗晚期非小细胞肺癌疗效的相关性研究

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (5): 555-560.

RRM1和ERCC1基因外周血中表达水平与吉西他滨联合铂类治疗晚期非小细胞肺癌疗效的相关性研究

徐浩锋¹, 王临润², 黄黎³, 吕燊³

¹浙江省富阳市人民医院, 富阳 311400,浙江;
²浙江大学医学院附属第一医院, 杭州 310003,浙江;
³浙江康恩贝制药股份有限公司,杭州 310052,浙江

收稿日期:2012-12-06 修回日期:2013-04-09 出版日期:2013-05-26 发布日期:2013-05-22
作者简介:徐浩锋,男,本科,副主任医师,主要从事临床药学工作。Tel: 13968161558 E-mail: xhfhj@sina.com

RRM1 and ERCC1 expressions and their relationship with gemcitabine and platinum in advanced non-small cell lung cancer

XU Hao-feng¹, WANG Lin-run², HUANG Li³, LV Shen³

¹Zhejiang Province Fuyang People's Hospital, Fuyang 311400, Zhejiang,China;
²The First Affiliated Hospital,Medicine College of Zhejiang University, Hangzhou 310003, Zhejiang, China;
³Zhejiang Conba Pharmaceutical CO.,LTD, Hangzhou 310052,Zhejiang,China

Received:2012-12-06 Revised:2013-04-09 Online:2013-05-26 Published:2013-05-22

摘要/Abstract

摘要： 目的: 探讨外周血中DNA修复基因RRM1(核苷酸还原酶,ribonucleotide reductase M1)和ERCCl(切除修复交叉互补组基因1,excision repair cross-complementation 1)的表达水平与吉西他滨联合铂类治疗非小细胞肺癌(Non-small-cell lung cancer, NSCLC)疗效的相关性。方法: SYBR荧光实时定量PCR检测NSCLC组织和外周血中RRM1和ERCC1 mRNA表达水平。分类变量之间进行χ²检验,连续性变量之间进行Spearman等级相关性分析;总体生存率的比较采用Kaplan-Meier生存曲线和log-rank检验。结果: 本研究中,34例晚期NSCLC患者外周血RRM1和ERCC1 mRNA表达水平进行了有效地检测,22例病例同时进行了肿瘤组织和外周血的基因检测。RRM1 mRNA 的相对表达量在外周血和肿瘤组织中存在线性相关性(R²=0.045,P=0.048),而ERCC1在两者之间无线性相关(R²=0.016,P=0.251)。RRM1低表达组的生存期(16.0月)明显长于高表达组(12.5 月)( Log-rank 3.980,P=0.046 )。而ERCC1的表达在两组间无统计学意义( P＞0.05)。结论: 研究表明,在入组的NSCLC患者中,外周血中RRM1低表达组的生存期明显长于高表达组,对化疗反应的有效率更高,其结果有助于筛选出接受吉西他滨联合铂类化疗方案的患者。

关键词: 非小细胞肺癌, 吉西他滨, RRM1, ERCC1

Abstract: AIM: To evaluate the predictive value of gene expression of ribonucleotide reductase M1 (RRM1) and excision repair cross-complementation 1( ERCCl ) in peripheral blood from Chinese patients with non-small-cell lung cancer (NSCLC) treated with gemcitabine plus platinum.METHODS: SYBR real-time PCR was used to determine the tumor tissue and peripheral blood RRM1 and ERCC1 mRNA expression levels in NSCLC patients. The χ² test was used to analyze categorical variables and Spearman rank correlation analysis was used to analyze continuous variables. Kaplan-Meier survival curves and the log-rank test were used for the comparison of overall survival rates.RESULTS: In the present study, 34 Chinese patients with histologically confirmed stages IIIB and IV NSCLC were recruited; the tumor tissue and peripheral blood gene expression levels were measured in 22 patients. Linear correlations were observed between peripheral blood and tumor tissue expression levels for RRM1 (R²=0.045, P=0.048), while no correlation was detected for ERCC1 (R²=0.016, P=0.251). Subjects with low peripheral blood RRM1 expression survived longer than those with high RRM1 expression (16.0 vs12.5 months, log-rank 3.980, P=0.046). The expression of ERCC1 showed no obvious differences between the two groups.CONCLUSION: The study demonstrates increased survival and superior efficacy of gemcitabine and cisplatin combination chemotherapy in the treatment of NSCLC patients with low peripheral blood RRM1 expression. The results contribute to the selection of patients who are most suitable for treatment with gemcitabine and cisplatin combination chemotherapy.

Key words: Non-small cell lung, Gemcitabine, RRM1, ERCC1

中图分类号:

R965.2

徐浩锋, 王临润, 黄黎, 吕燊. RRM1和ERCC1基因外周血中表达水平与吉西他滨联合铂类治疗晚期非小细胞肺癌疗效的相关性研究[J]. 中国临床药理学与治疗学, 2013, 18(5): 555-560.

XU Hao-feng, WANG Lin-run, HUANG Li, LV Shen. RRM1 and ERCC1 expressions and their relationship with gemcitabine and platinum in advanced non-small cell lung cancer[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(5): 555-560.

参考文献

[1] Jing YF, Wang Y. The development of predicting the lung cancer prognosis and resistance to gemcitabine by the expression level of RRM1[J]. J Clin Pulmon Med, 2008, 13(10): 1268-1270.
[2] Wang LR, Zhang GB, Chen J, et al. RRM1 gene expression in peripheral blood is predictive of shorter survival in Chinese patients with advanced non-small-cell lung cancer treated by gemcitabine and platinum[J]. J Zhejiang Univ Sci , 2011,12(3):174-179.
[3] Olaussen KA , Dunant A, Fouret P, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy[J]. N Engl J Med, 2006, 355(10): 983 - 991.
[4] Olaussen KA , Fouret P, Kroemer G. ERCC1-specific immunostaining in non-small-cell lung cancer[J]. N Engl J Med, 2007, 357(15): 1559- 1561.
[5] Wang LR, Huang MZ, Zhang GB, et al. Phase Ⅱ study of gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer [J]. Canc Chemother Pharmacol, 2007, 60(4): 601-607.
[6] Wang LR, Wu XH, Huang MZ, et al. The efficacy and relationship between peak concentration and toxicity profile of fixed-dose-rate gemcitabine plus carboplatin in patients with advanced non-small-cell lung cancer [J]. Canc Chemother Pharmacol, 2007, 60(2): 211-218.
[7] Soo RA, Wang LZ, Tham LS, et al. A multicentre randomised phase II study of carboplatin in combination with gemcitabine at standard rate or fixed dose rate infusion in patients with advanced stage non-small-cell lung cancer[J]. Ann Oncol, 2006, 17(7): 1128-1133.
[8] Ceppi P, Volante M, Novello S, et al. ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine [J]. Ann Oncol, 2006, 17(12): 1818-1825.
[9] Bergman AM, Eijk PP, Ruiz Van Haperen VW, et al. In vivo induction of resistance to gemcitabine results in increased expreasion of ribonucleotide reductase subunit M1 as the major determinant[J]. Cancer Res, 2005,65(20): 9510-9516.
[10] Bepler G, Kusmartseva I, Sharma S, et al. RRM1 modulated In vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer[J]. J Clin Oncol, 2006, 24(29): 4731-4737.
[11] 刘瑞吉,刘兰吉. 非小细胞肺癌组织中ERCC1、BRCA1的表达变化及意义[J]. 山东医药,2010, 50(38):578-582.
[12] 单利,韩志刚,刘莉,等. 晚期非小细胞肺癌ERCC1和BRCA1的表达及与顺铂耐药性的临床研究[J]. 肿瘤, 2009, 29(6): 147-151.

[1]	何杨, 杨魁, 栾家杰. CDA-G208A基因多态性对吉西他滨一线治疗肺鳞癌的疗效影响[J]. 中国临床药理学与治疗学, 2023, 28(3): 299-306.
[2]	张威, 王鸿渊, 雷晓航, 赵英帅, 吕炜超, 张建国. 中高危膀胱癌应用卡介苗+吡柔比星与卡介苗+吉西他滨预防术后复发的效果及对血清AGR、PON1的影响[J]. 中国临床药理学与治疗学, 2023, 28(10): 1146-1153.
[3]	黄小明, 杜野, 林少明, 沈观乐. 呼吸道微生态对晚期非小细胞肺癌患者接受PD-1抑制剂单药治疗疗效影响的探索性研究[J]. 中国临床药理学与治疗学, 2023, 28(1): 66-74.
[4]	张可心, 贾文静, 崔佳文, 敖路遥, 周芳, 王广基, 刘嘉莉. 第三代EGFR酪氨酸激酶抑制剂在非小细胞肺癌临床治疗中的应用及研究进展[J]. 中国临床药理学与治疗学, 2022, 27(9): 1016-1030.
[5]	叶小弟, 缪云萍, 陈爱瑛, 程敏, 田雪君, 郑高利. 裸鼠原位非肌层浸润性膀胱癌模型的优选及验证[J]. 中国临床药理学与治疗学, 2022, 27(4): 473-480.
[6]	裴清华, 孙建立. 奥希替尼获得性耐药的研究进展[J]. 中国临床药理学与治疗学, 2021, 26(1): 105-112.
[7]	魏为添, 陈晟, 汪亮, 曾剑. 灯盏花素对非小细胞肺癌A549细胞的促凋亡作用[J]. 中国临床药理学与治疗学, 2020, 25(6): 618-624.
[8]	王海莉，巩天晓，周士霞，梅家转，张中冕. 甲磺酸阿帕替尼三线治疗晚期非小细胞肺癌患者的疗效及安全性分析[J]. 中国临床药理学与治疗学, 2019, 24(5): 567-572.
[9]	杨科，李峻岭，杜斌，田中秋，景秀娟. 白蛋白结合型紫杉醇二线及以上治疗晚期非小细胞肺癌的单臂、单中心探索性临床研究[J]. 中国临床药理学与治疗学, 2019, 24(11): 1281-1286.
[10]	王海霞，刘兴安，侯继院，龚哲，单国用. KDR基因遗传变异对贝伐珠单抗一线治疗晚期非小细胞肺癌患者临床疗效的影响[J]. 中国临床药理学与治疗学, 2018, 23(7): 802-808.
[11]	李伟文，黎媛，孙蕾，黄公才，赵中伟. 艾迪注射液对培美曲塞联合奈达铂治疗晚期非小细胞肺癌的增效作用[J]. 中国临床药理学与治疗学, 2018, 23(3): 325-328.
[12]	高中原，孙更，李敏，谌茜，李萍，王雪融. 柚皮苷通过下调p70S6K抑制非小细胞肺癌细胞生长的作用机制研究[J]. 中国临床药理学与治疗学, 2017, 22(7): 762-766.
[13]	容国义，王淑美，唐末. 中医化痰法治疗非小细胞肺癌疗效的Meta分析[J]. 中国临床药理学与治疗学, 2017, 22(7): 787-794.
[14]	王宛明，董贾中，管淑敏. 泛素特异性肽酶22诱导胰腺癌细胞对吉西他滨耐药的观察[J]. 中国临床药理学与治疗学, 2017, 22(4): 412-417.
[15]	尤匡掌，陈斌，包倩倩. 七氟烷联合丙泊酚对老年非小细胞肺癌胸腔镜切除术后认知功能及血清氧化应激水平的影响[J]. 中国临床药理学与治疗学, 2017, 22(2): 190-193.