摘要
目的吉西他滨联合顺铂是治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的一线化疗方案,但其有效率仅20%~40%,其较低的化疗有效率与肿瘤耐药相关。研究NSCLC组织中切除修复交叉互补基因1(exeision repair cross-compietionl1,ERCC1)和乳腺癌易感基因1(breast cancer susceptibility gene-1,BRCA1)mRNA的表达及其与铂类化疗敏感性的关系。方法应用实时荧光定量PCR技术检测2009-03-01-2011-04-16武汉钢铁(集团)公司第二职工医院收集的98例晚期NSCLC患者中ERCC1和BRCA1mRNA的表达情况,分析其与含铂联合治疗方案化疗耐药性的关系。结果检测98例患者中ERCC1和BRCA1mRNA的相对表达量,其中位数分别为0.048和0.011,四分位间距IQR分别为0.0058和0.001。ERCC1mRNA的高表达率为56.1%(55/98),其表达在不同性别、年龄、组织学类型及临床分期中差异无统计学意义,P>0.05;BRCA1mRNA的高表达率为64.3%(63/98),其表达在不同性别、年龄、组织学类型及临床分期中差异无统计学意义,P>0.05。在ERCC1mRNA低表达组GP方案化疗客观缓解率为48.8%(21/43),而在高表达组化疗客观缓解率为29.1%(16/55),两组之间比较差异有统计学意义,χ~2=4.0,P=0.045;在BRCA1mRNA低表达组GP化疗客观缓解率为57.1%(20/35),在高表达组GP化疗客观缓解率为28.6%(18/63),差异有统计学意义,χ~2=7.74,P=0.005;ERCC1和BRCA1 mRNA联合低表达组中GP化疗客观缓解率为70.4%(19/27),而其联合高表达组GP化疗客观缓解率仅为21.1%(8/38)。结论 ERCC1、BRCA1mRNA高表达患者在使用含铂化疗方案时疗效差,提示ERCC1和BRCA1 mRNA高表达NSCLC患者对铂类具有耐药性。ERCC1和BRCA1mRNA联合低表达患者在使用含铂方案化疗时有效率更高,提示应用ERCC1和BRCA1mRNA联合检测时,患者可获得更大的益处。
OBJECTIVE Gemcitabine combined with cisplatin is the first-line chemotherapy regimen for patients with advanced non-small cell lung cancer,but its effective rate is only 20%-40%,the low effective rate of chemotherapy is related to the drug resistance.This research aimed to study the expression of ERCC1 and BRCA1in non-small-cell lung cancer tissues and the relationship between the genes expression and the sensitivity to platinum based chemotherapy.METHODS The expression of ERCC1 and BRCA1in 98 advanced NSCLC cases were detected by RT-PCR during the period from March 2009 to April 2011 in the second hospital of Wuhan Iron and Steel Corporation.The relationship between the expression of ERCC1 and BRCA1mRNA and the sensitivity of platinum based chemotherapy were explored.RESULTS The relative expression levels of ERCC1 and BRCA1mRNA were detected in 98 patients,the median numbers were 0.048 and 0.011,respectively,the interquartile range were 0.005 8and 0.001.The high expression rate of ERCC1 and BRCA1was respectively 64.3%(55/98)and 64.3%(63/98).The positive expression of ERCC1 and BRCA1had no significant correlation with gender,age,clinical stages and histological types(P〈0.05).GP chemotherapy ORR of ERCC1(21,48.8%)and BRCA1(20,57.1%)low expression group was significantly higher than that of ERCC1(16,29.1%)and BRCA1(18,28.6%)high expression group,(χ^2=4.0,P=0.045;χ^2=7.74,P=0.005).In ERCC1 and BRCA1joint-low expression group,the response rate was up to 19(70.4%),while in its joint high-expression group GP chemotherapy ORR was only 8(21.1%).CONCLUSIONS BRCA1 and ERCC1low expression patients had a better therapeutic effect in the use of Platinum containing chemotherapy,it suggested that NSCLC patients with high expression of ERCC1 and BRCA1have platinum resistance.At the same time,patients with low expression of ERCC1 and BRCA1have better curative effect when treated with platinum containing chemotherapy.suggesting that patients can get more benefits when ERCC1 and BRCA1joint detection were performed.
出处
《中华肿瘤防治杂志》
CAS
北大核心
2017年第3期178-182,共5页
Chinese Journal of Cancer Prevention and Treatment
基金
武汉市临床医学科研项目(WX14C28)
作者简介
徐向勇,男,湖北武汉人,副主任检验技师,主要从事基因扩增和临床基础检验的研究工作。Tel:86—27—86213111 E-mail:13260516526@163.com
【通讯作者简介】王清,男,湖北武汉人,副主任医师,主要从事肿瘤化放疗的研究工作。Tel:86-27-86213003 E-mail:575847321@qq.com