期刊文献+

晚期非小细胞肺癌肿瘤组织和外周血淋巴细胞中RRM1和ERCC1基因表达的研究 被引量:2

Expression of RRM1 and ERCC1 genes in tumor tissues and peripheral blood lymphocytes of advanced non-small cell lung cancer
暂未订购
导出
摘要 目的:探讨晚期非小细胞肺癌(NSCLC)肿瘤组织和外周血淋巴细胞中RRM1、ERCC1基因表达水平及其临床意义。方法:应用实时荧光定量PCR技术检测49例晚期NSCLC肿瘤组织和外周血淋巴细胞中RRM1、ERCC1 mRNA表达水平,对照分析其与患者临床特征、吉西他滨/卡铂方案的化疗反应以及预后的关系。结果:肿瘤组织和外周血淋巴细胞中RRM1表达水平呈正相关(rs=0.332,P<0.05),而ERCC1无相关(rs=0.258,P>0.05);肿瘤组织或外周血淋巴细胞中RRM1和ERCC1表达几乎同步(rs=0.634、0.351,P<0.05),但基因表达与患者的性别、年龄、吸烟状态、体力状况PS评分,以及肿瘤临床分期和组织学类型均无显著相关性(P均>0.05)。肿瘤组织中RRM1、ERCC1或外周血RRM1低表达者化疗有效率、中位生存期及1年生存率均高于高表达者,两者比较差异均有统计学意义(P<0.05),特别是肿瘤组织ERCC1低表达者有较高的2年生存率(P<0.05);而外周血ERCC1表达水平与化疗疗效以及预后均无相关性(P均>0.05)。结论:肿瘤组织中RRM1、ERCC1和外周血淋巴细胞中RRM1基因表达水平可能与晚期NSCLC患者吉西他滨/卡铂化疗的疗效以及预后密切相关。 Objective: To investigate the expression of RRM1 and ERCC1 genes in tumor tissues and peripheral blood lymphocytes of advanced non-small cell lung cancer(NSCLC).Methods: Tissue and peripheral blood samples were collected from 49 advanced NSCLC patients treated with gemcitabine plus carboplatin.The expressions of RRM1 and ERCC1 mRNA in tumor tissue and peripheral lymphocytes were detected by real-time fluorescent quantitative PCR.The relationship of gene expression with clinical characteristics,chemotherapy response and prognosis was analyzed.Results: The RRM1 expression in tumor tissues was positively correlated with that in peripheral blood lymphocytes,while no significant correlation was observed between ERCC1 expression in tumor tissues and that in peripheral blood(rs=0.332 and 0.258;P=0.020 and 0.073,respectively).The expression of RRM1 and ERCC1 in tumor tissues peripheral lymphocytes was synchronous(rs=0.634 and 0.351;P0.001 and 0.013,respectively).There was no significant correlation of gene expression with gender,age,smoking status,performance status,clinical stages and histological types of patients(P0.05).Significant difference was found in response rate to chemotherapy(P0.05,P0.01,P0.05),median survival time(P0.05,P0.01,P0.05) and 1-year survival rate(P0.01,0.05,P0.05) between patients with low RRM1 and ERCC1 expression levels in tumor tissues or low RRM1 expression levels in peripheral blood and those with high RRM1 and ERCC1 expression levels.The patients with low ERCC1 expression levels in tumor tissues gained higher 2-year survival rate(P0.05).There was no correlation of the expression of ERCC1 in peripheral blood with the response to chemotherapy and prognosis(P0.05).Conclusion: The expression of RRMI and ERCC1 genes in tumor tissues and RRM1 in peripheral blood lymphocytes is closely correlated with the response to chemotherapy and prognosis of patients with advanced NSCLC treated with gemcitabine plus carboplatin.
出处 《浙江大学学报(医学版)》 CAS CSCD 北大核心 2012年第5期540-546,共7页 Journal of Zhejiang University(Medical Sciences)
基金 浙江省医药卫生科学研究基金计划(2008A060) 浙江省科技计划资助项目(2009C33165) 浙江省中医药普通课题研究计划(2009CA061)
关键词 非小细胞肺/病理学 肺肿瘤/病理学 聚合酶链反应 核苷酸还原酶类/生物合成 DNA结合蛋白质类/生物合成 脱氧胞苷/治疗应用 脱氧胞苷/类似物和衍生物 卡铂/治疗应用 基因表达 Carcinoma non-small-cell lung/pathology Lung neoplasms/pathology Polymerase chain reaction Ribonucleotide reductases/biosynthesis DNA-binding proteins/biosynthesis Deoxycytidine/therapeutic use Deoxycytidine/analogs & derivatives Carboplatin/therapeutic use Gene expression
  • 相关文献

参考文献16

  • 1JEMAL A, SIEGEL R, WARD E, et al. Cancer statistics 2009 [ J ]. CA Cancer J Clin, 2009,59 (4) :225-249.
  • 2GOSSAGE L, MADHUSUDAN S. Current status of excision repair cross complementing-group 1 (ERCC1) in cancer [ J ]. Cancer Treat Rev, 2007,33 (6) : 565-577.
  • 3OLAUSSEN K A, FOUTET P, KROEMER G. ERCCl-specific immunostaining in non-small-cell lung cancer [J]. N Engl J Meal,2007,357(15) : 1559- 1561.
  • 4WANG X, ZHAO J, YANG L, et al. Positive expression of ERCC1 predicts a poorer platinum- based treatment outcome in Chinese patients with advanced non-small-cell lung cancer [ J ]. Meal Onco1,2010,27 ( 2 ) :484-490.
  • 5BEPLER 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.
  • 6ROSELL R, DANENBERG K D, ALBEROLA V, et al. Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin- treated advanced non-small cell lung cancer patients [ J ]. Clin Cancer Res, 2004,10 ( 4 ) : 1318-1325.
  • 7LEE J J, MAENG C H, BAEK S K, et al. The immunohistochemical overexpression of ribonu- eleotide reduetase regulatory subunit M1 (RRM1) protein is a predictor of shorter survival to gemcitabine-based chemotherapy in advanced non-small-cell lung cancer ( NSCLC ) [ J ]. Lung Cancer,2010,70 (2) :205-210.
  • 8WANG L R, HUANG M Z, ZHANG G B, et al. Phase 1I study of gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer [ J ]. Cancer Chemotherapy and Pharmacology, 2007,60(4) :601-607.
  • 9陈建,李敏伟,张国兵,李菌,王临润.SYBR荧光实时定量PCR检测非小细胞肺癌组织与外周血中RRM1和ERCC1及BRCA1基因表达水平[J].浙江大学学报(医学版),2010,39(6):628-633. 被引量:8
  • 10HERRICK J, SCLAVI B. Ribonucleotide reductase and the regulation of DNA replication:an old story and an ancient heritage [ J ]. Mol Microbiol, 2007,63 ( 1 ) : 22-34.

二级参考文献22

  • 1董嵩,吴一龙,郭爱林,陈志红,谢至,林嘉颖,张绪超.荧光实时定量PCR检测非小细胞肺癌组织及外周血中RRM1 mRNA表达水平的方法[J].肿瘤,2007,27(7):577-581. 被引量:4
  • 2Wachters FM,Wong LS,Timens W,et al.ERCC1,hRad51,and BRCA1 protein in relation to tumour response and survival of stage Ⅲ/Ⅳ NSCLC patients treated with chemotherapy[J].Lung Cancer,2005,50(2):211-219.
  • 3Bartels CL,Lambert MW.Domains in the XPA protein important in its role as a processivity factor[J].BBRC,2007,356(1):219-225.
  • 4Gossage L,Madhusudan S.Current status of excision repair cross complementing-group 1(ERCC1) in cancer[J].Cancer Treat Rev,2007,33:565-577.
  • 5Zhou W,Liu G,Park S,et al.Gene smoking interaction associations for the ERCC1 polymorphism in the risk of lung cancer[J].Cancer Epidermal Biomarkers Prev,2005,14(2):491-496.
  • 6Lord RV,Brabender J,Gandara D,et al.Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small-cell lung cancer[J].Clin Cancer Res,2002(8):2286-2291.
  • 7Bepler G,Li X,Schell M,et al.Predictive value of RRM1 and ERCC1 protein level in a prospective community-based trial of gemcitabine/carboplatin versus gemcitabine alone[abstract].J Clin Oncol,2008,26:8033.
  • 8Simon GR,Sharma S,Cantor A,et al.ERCC1 expression is a predictor of survival in resected patients with non-small cell lung cancer[J].Chest,2005,127(3):978-983.
  • 9Zheng Z,Chen T,Li X,et al.DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer[J].N Engl J Med,2007,356(8):800-808.
  • 10Davidson JD,Ma L,Flagella M,et al.An increase in the expression of ribonucleotide reductase large subunit 1 is associated with gemcitabine resistance in non-small cell lung cancer cell lines[J].Cancer Res,2004,64(11):3761-3766.

共引文献10

同被引文献7

二级引证文献17

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部