非小细胞肺癌组织BRCA1、ERCC1、RRM1表达与肿瘤体外药敏相关性的研究

Study on the relationship between BRCA1、ERCC1、RRM1 protein expression and sensitivity of non-small-cell lung cancer to chemotherapeutic drug in vitro

目的:探讨非小细胞肺癌组织乳腺癌易感基因1(breast cancer susceptibility gene1,BRCA1)、切除修复交叉互补基因1(excision repair cross-complementing gene1,ERCC1)、核苷酸还原酶M1亚基(ribonucleotide reductase M1,RRM1)蛋白表达与肿瘤体外药敏的相关性,为非小细胞肺癌个体化治疗提供预测指标。方法:收集32例非小细胞肺癌患者手术切除的新鲜标本,采用ATP-TCA方法检测紫杉醇、顺铂、吉西他滨体外药敏;采用免疫组化PV方法检测BRCA1、ERCC1、RRM1蛋白表达。结果:BRCA1高表达18例(56.2%),低表达14例(43.8%),BRCA1高表达组紫杉醇有效13例(72.2%),BRCA1低表达组有效4例(28.6%)(P<0.05);ERCC1高表达13例(40.6%),低表达19例(59.4%),ERCC1高表达组顺铂有效2例(15.4%),ERCC1低表达组有效11例(57.9%)(P<0.05);RRM1高表达15例(46.9%),低表达17例(53.1%),RRM1高表达组吉西他滨有效3例(20.0%),RRM1低表达组有效10例(58.8%)(P<0.05)。结论:BRCA1、ERCC1、RRM1蛋白表达水平和紫杉醇、顺铂、吉西他滨体外药物敏感性具有相关性,联合检测为非小细胞肺癌筛选化疗药物提供更加可靠的依据。

Objective To explore the relationship between BRCA1 ,ERCCI ,RRM1 protein expressions of non-small-celllung cancer and sensitivity of the cancer to chemotherapeutic drug in vitro, and provide prognostic markers to guide individu-al chemotherapy in non-small-cell lung cancer field. Methods： 32 fresh operative non-small-cell lung cancer samples werecollected and immediately were used to be tested the sensitivity to paclitaxel, cisplatin, gemcitabine with the method of ATP-tumor chemosensitivity assay;detected expressions of BRCA1, ERCC1, RRM1 in 32 cases of non-small-cell lung cancerparMfin-embedded pathological specimens by means of immunohistochemical analysis（PV method）. Results： There were 18（56.3%）eases with the high level of BRCA1 protein expression, and still another 14 cases（43.8%） with the low level of BR-CA1 protein expression, there were 13 cases（72.2%） with sensitive to paclitaxel in the high level of BRCA1 protein expres-sion group,and 4 sensitive cases （28.6%） in the low level of BRCA1 protein expression group （P〈0.05）. There were 13cases（40.6%） with the high level of ERCC1 protein expression, and still another 19 cases（59.4%） with the low level of ERCC1protein expression, there were 2 cases（15.4%） with sensitive to cisplatin in the high level of ERCC1 protein expressiongroup,and 11 sensitive cases（57.9%） in the low level of ERCC1 protein expression group（P〈O.05）. There were 15 cases（46.9%） with the high level of RRM1 protein expression, and still another 17 cases（46.9%） with the low level of RRM1protein expression, there were 3 cases（20.0%） with sensitive to gemcitabine in the high level of RRM1 protein expressiongroup,and 10 sensitive cases（58.8%） in the low level of RRM1 protein expression group（P〈O.OS）.Conclusion： There is arelevance between BRCA1 ,ERCC1 ,RRM1 protein expressions of non-small-cell lung cancer and its sensitivity to paclitax-el ,cisplatin,gemcitabine in vitro. A combined test with this two methods may be useful in providing more reliable evidence tochoose chemotherapeutic drug in non-small-cell lung cancer field.