晚期非小细胞肺癌组织ERCC1和BRCA1表达与铂类化疗敏感性临床研究

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BRCA1 mRNA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BRCA1 mRNA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.ERCC1 mRNA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;BRCA1 mRNA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ERCC1 mRNA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,x2 =4.0,P=0.045;在BRCA1 mRNA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,x2 =7.74,P=0.005;ERCC1和BRCA1 rnRNA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、BRCA1 mRNA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BRCA1 mRNA联合检测时,患者可获得更大的益处.

Expression of ERCC1 and BRCA1 in tissues of advanced non-small-cell lung cancer and its relationship with the sensitivity of platinum based chemotherapy

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 BRCA1 in 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 BRCA1 in 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 be tween the expression of ERCC1 and BRCA1 mRNA and the sensitivity of platinum based chemotherapy were explored.RESULTS The relative expression levels of ERCC1 and BRCA1 mRNA were detected in 98 patients,the median numbers were 0.048 and 0.011,respectively,the interquartile range were 0.005 8 and 0.001.The high expression rate of ERCC1 and BRCA1 was respectively 64.3 ％ (55/98) and 64.3％ (63/98).The positive expression of ERCC1 and BRCA1 had 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,(x2 =4.0,P=0.045;x2 =7.74,P=0.005).In ERCC1 and BRCA1 joint-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 ERCC1 low 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 BRCA1 have platinum resistance.At the same time,patients with low expression of ERCC1 and BRCA1 have better curative effect when treated with platinum containing chemotherapy.suggesting that patients can get more benefits when ERCC1 and BRCA1 joint detection were performed.