恶性胸腹水中肿瘤细胞BRCA1和β-tubulin Ⅲ的表达与多西紫杉醇药物敏感性的关系  

Relationship between mRNA expression of BRCA1 and β-tubulin Ⅲ in malignant effusions and ex vivo chemosenstitivity to docetaxel

作　　者：王立峰[1] 张微[2] 钱晓萍[1] 胡静[1] 禹立霞[1] 邹征云[1] 胡文静[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,江苏南京210008 [2]南京中医药大学附属江苏省中医院肿瘤内科,江苏南京210029

出　　处：《现代肿瘤医学》2011年第8期1496-1500,共5页Journal of Modern Oncology

基　　金：南京市卫生局科研基金资助项目(编号:YKK10072)

摘　　要：目的:疗效相关分子生物标记的探索是实现个体化治疗的关键所在。由于肿瘤原发灶与转移灶肿瘤细胞在分子水平的显著差异及转移性恶性肿瘤的难治性,本研究旨在探索肿瘤特殊转移灶即恶性胸/腹水中肿瘤细胞的BRCA1和β-tubulinⅢmRNA表达水平与多西紫杉醇(TXT)药物敏感性的关系。方法:前瞻性地收集41例进展期肿瘤的恶性胸水/腹水,分离肿瘤细胞后ATP-TCA方法检测TXT敏感性;实时荧光定量RT-PCR检测的BRCA1和β-tubulinⅢmRNA表达。结果:在非小细胞肺癌(NSCLC)组(P=0.008)和胃癌组(P=0.032)的恶性胸/腹腔积液中肿瘤细胞的BRCA1 mRNA表达与TXT体外药物敏感正相关。β-tubulinⅢmRNA表达仅在NSCLC患者的恶性胸腔积液中肿瘤细胞与TXT药物敏感负相关(P=0.022)。联合检测BRCA1和β-tubulinⅢ对于TXT药物敏感性的预测没有交互作用(P>0.05)。结论:在NSCLC和/或胃癌患者的恶性胸/腹腔积液中,BRCA1和β-tubulinⅢ表达与TXT敏感性相关且前者可能比后者更有意义。对于伴有恶性积液的进展期NSCLC和/或胃癌患者,恶性积液有可能成为一合适的标本进行分子生物标记的检测。Objective：Despite the success of docetaxel as an anti-tumor agent,the inter-individual variability in drug response still poses a major impediment on further use of this agent in the treatment of cancer.As some patients are inherent or acquired-resistance to this drug,biomarkers are desired to stratify patients into groups of different likelihood of the tumor response before chemotherapy,thus maximizing effects and minimizing toxicities of chemotherapy.Our current study focus on two promising biomarkers,BRCA1（breast cancer susceptibility gene 1） and β-tubulin Ⅲ.To investigate their potential role in serving as biomarkers for drug sensitivity in cancer patients with metastases,we statistically measure the mRNA expression level of ERCC1 and BRCA1 in tumor cells isolated from malignant effusions and correlate them with docetaxel sensitivity.Methods： Real-time quantitative PCR was used to test related genes expression in forty-one malignant effusions prospectively collected.Viable tumor cells obtained from malignant effusions were tested for sensitivity to docetaxel using ATP-TCA assay.Results： BRCA1 expression level was positively correlated with sensitivity to docetaxel in non small cell lung cancer（NSCLC）（P=0.008） and gastric cancer patients（P=0.032）,meanwhile β-tubulin Ⅲ expression level was inversely correlated with sensitivity to doxetaxel in malignant effusions of NSCLC patients（P=0.022）.No significant interaction was found between BRCA1 and β-tubulin Ⅲ mRNA expressions on sensitivity to docetaxel（P0.05）.Conclusion： Our results demonstrated that BRCA1 and β-tubulin III mRNA expression level in malignant effusions,in which all cancer cells were metastatic,were correlated with docetaxel sensitivity.Meanwhile,BRCA1 may be a better predictive marker for chemosensitivity to doxetaxel than β-tubulin Ⅲ.At the cost of a centesis,it may be possible to acquire a limited genomic portrait of tumor in some patients with malignant effusions,enabling the development of ＂real-tim

关 键 词：个体化疗 BRCA1 Β-TUBULIN Ⅲ 恶性渗出液 

分 类 号：R730.53[医药卫生—肿瘤] R734.3[医药卫生—临床医学]