恶性胸腔和腹腔积液中ERCC1和BRCA1 mRNA的表达水平与顺铂敏感性的关系  

ERCC1 and BRCA1 mRNAs expression levels in malignant pleural and peritoneal effusions are associated with chemosensitivity to cisplatin in vitro

作　　者：王立峰[1] 殷海涛[1] 钱晓萍[1] 胡文静[1] 邹征云[1] 禹立霞[1] 刘宝瑞[1] 

机构地区：[1]南京大学医学院附属鼓楼医院肿瘤中心暨南京大学临床肿瘤研究所,南京210008

出　　处：《肿瘤》2010年第3期226-231,共6页Tumor

基　　金：南京市医学科技发展重点资助项目(ZKX05015;ZKX06021)

摘　　要：目的:本研究旨在探讨肿瘤特殊转移灶恶性胸腔/腹腔积液中核苷酸切除修复交叉互补组1(excision repair cross-complementing group 1,ERCC1)基因和乳腺癌易感基因1(breast cancer 1,BRCA1)的表达水平与顺铂体外药物敏感性之间的关系。方法:前瞻性收集46例Ⅳ期恶性肿瘤患者的恶性胸腔/腹腔积液,分离出肿瘤细胞后,采用体外药敏试验三磷酸腺苷生物荧光法检测(adenosine triphosphate-bioluminescence assay,ATP-TCA)法检测肿瘤细胞对顺铂的药物敏感性,实时荧光定量PCR检测ERCC1和BRCA1 mRNA的相对表达水平。结果:在非小细胞肺癌患者的恶性胸腔/腹腔积液中,肿瘤细胞的ERCC1 mRNA相对表达水平与顺铂抗药性呈正相关(P=0.001,r=0.685)。非小细胞肺癌患者(P=0.014,r=0.541)和胃癌患者(P=0.002,r=0.625)恶性胸腔/腹腔积液中肿瘤细胞的BRCA 1 mRNA相对表达水平与顺铂抗药性呈正相关。ERCC1和BRCA1对顺铂药物敏感性的影响存在交互作用(所有患者P=0.010;胃癌患者P=0.027)。结论:恶性胸腔/腹腔积液中肿瘤细胞的ERCC1和BRCA1 mRNA的相对表达水平与顺铂体外药物敏感性相关。联合检测ERCC1和BRCA1这2种基因较只采用其中一种基因在预测顺铂药物敏感性方面的价值更大。Objective：The aim of this study was to investigate the association of mRNA expressions of ERCC1（excision repair cross-complementing group 1） and BRCA1（breast cancer 1） with chemosensitivity to cisplatin in malignant pleural and peritoneal effusions.Methods：Malignant pleural and peritoneal effusions were collected from 46 patients diagnosed with stage Ⅳ malignant tumor,prospectively.The tumor cells were isolated and the sensitivity of tumor cells to cisplatin was detected by adenosine triphosphate-bioluminescence assay（ATP-TCA）.Real-time quantitative PCR was used to determine the mRNA expressions of ERCC1 and BRCA1.Results：The expression level of ERCC1 mRNA was negatively correlated with sensitivity of non-small cell lung cancer（NSCLC） to cisplatin（P= 0.001,r=0.685）.BRCA1 mRNA expression level had negative correlation with sensitivity to cisplatin in both NSCLC（P=0.014,r=0.541） and gastric cancer（P=0.002,r=0.625）.A significant interaction was found between the effects of ERCC1 and BRCA1 mRNA expressions on sensitivity to cisplatin（P=0.010 for all patients;P=0.027 for gastric cancer patients）.Conclusion：ERCC1 and BRCA1 mRNA expression levels correlated with ex vivo chemosensitivity of tumor cells to cisplatin in malignant pleural and peritoneal effusions.Detection of both ERCC1 and BRCA1 may have a higher reliability in predicting the sensitivity of tumor cells to cisplatin than detection of single ERCC1 or BRCA1 expression.

关 键 词：癌 胸腔积液 恶性 腹水 恶性 核苷酸切除修复 基因 ERCC1 基因 BRCA1 顺铂 药物筛选试验 抗肿瘤 

分 类 号：R730.53[医药卫生—肿瘤]