摘要
目的探讨DNA修复基因ERCC1单核苷酸多态性(SNP)与非小细胞肺癌(NSCLC)铂类药物化疗后的预后关系。方法经病理学确诊的晚期NSCLC患者120例,采用铂类为主的两药联合化疗方案,化疗前采集患者外周血。采用基因芯片法检测ERCC1(118)、(504)的SNP,并随机抽取10%的样本进行基因测序来验证该方法的准确性,比较不同基因型与铂类药物化疗后生存期的关系。结果成功进行基因分型,野生型、杂合型和突变型的叠加荧光分别显示为绿色、黄色和红色,与基冈测序结果完全吻合。中位随访时间11个月。携带ERCCl(118)C/C、C/T+rr/T基凶型患者铂类药物化疗后中位牛存期(MSq、),1年、2年及3年牛存率分别为10.9个月、35.9%、6.3%、1.6%和13.5个月、59.5%、19.0%、14.3%,2组间差异均有统计学意义(P〈0.05或P〈0.01);携带ERCC1(504)C/C基因型、C/A+,A/A基因型1年生仔率、2年牛存率分别为66.7%、16.8%和31.3%、7.8%,2组间差异均有统计学意义(P〈0.05或P〈0.01),而MST和3年生存率2组间差异尤统计学意义(P〉0.05)。结论 该芯片检测方法准确,高通量,价卡2}低廉,适用于大规模样本SNP检测,ERCC1(118)基因多态性与NSCLC患者铂类约物化疗后的生存期有关,有可能作为铂类约物化疗后生存期的预测指标。
Objective To investigate the relationship between genetic polymorphisrns of excision repair cross - eom- plementation group 1 (ERCC1) and survival of patients with advanced non -small cell lung cancer (NSCLC) treated with platinum - based chemotherapy. Methods A total of 120 patients with advanced NSCI,C were routinely treated by cisplatin - or carboplatin - hosed chemotherapy, The polymorphie genotypes were analyzed by gene - chip method using DNA samples isolated from peripheral blood before treatment. Besides, 10% samples were extracted randomly for se- quencing to test the accuracy of this method. To explored the association between single nueleotide polymorphism (SNP) of ERCCI (118) ,ERCCI (504) and progrmsis In plat inmn- based chemotherapy in advanced NSCLC patients. Results Homozygous wild type, heterozygote type and hemozyguus mutant type yielded green, yellow and red fluorescence, re- spectively, the resuhs were according to gene sequencing. Median follow - up period was l l months. Mean survival time ( MST), 1 - year survival ,2 - year survival and 3 - year survival rates of patients with the ERCCI ( 118 ) C/C genotype, C/T + T/T genotype were 10.9 months, 35.9% , 6.3% , and 1.6% vs. 13.5 months, 59.5% , 19.0% , and 14.3% , respectively, with significant difference( P 〈 0.05 or P 〈 0.01 ). 1 - year survival , 2 - year survival rate of patients with the ERCC1 (504) C/C genotype and C/A + A/A genotype were 66.7%, 16.8% vs. 31.3%, 7.8% ,respectively, with signiticant difference( P 〈 0.05 ). MST and 3 - year survival rates were no significant difference(P 〉 0.05 ). Conclusion The DNA mieroan'ay - based method is accurate, high - throughput and inexpensive, suitable for SNP genotyping in a large number of samples. Polymorphisms of ERCC1 (118) mlight be associated with overall survival period in patients with advanced NSCLC after treatmem with platin - based chemotherapy, which might be the predictive markers for overall survival.
出处
《徐州医学院学报》
CAS
2011年第9期620-624,共5页
Acta Academiae Medicinae Xuzhou
基金
汀苏省自然科学基金前期预研项目(BK2005203)
南京市医学科技发展重点项目基金(ZKX05030)
关键词
肺肿瘤
非小细胞肺癌
化学疗法
基因型
生存期
单核苷酸多态性
基因芯片
lung neoplasms
non - small cell lung cancer
chemotherapy
genolype
survival period
single nacleotide polymorphism
gene chip