摘要
目的研究细胞色素P450 3A4(CYP3A4)在乳腺癌组织中的表达及其与化疗反应间的关系,并对其表达差异的遗传基础进行初步探讨。方法乳腺癌病例组包括40例单纯手术患者3、6例新辅助化疗后手术患者和200例辅助性化疗患者;其中新辅助化疗患者接受以紫杉醇为基础的化疗。利用实时荧光RT-PCR检测手术患者癌组织及其癌旁组织中CYP3A4 mRNA的表达,连接依赖性SNP技术检测CYP3A4*18基因分型。结果 CYP3A4在大多数乳腺癌组织及其癌旁组织中均有表达;在40例单纯手术患者中,其表达水平(ΔCt)分别为21.8(18.7-24.2)和21.3(18.0-23.1);36例新辅助化疗患者中,其表达水平分别为20.7(16.2-24.7)和21.1(17.0-23.8);癌与癌旁组织间的比较无统计学差异(P<0.05)。新辅助化疗有反应者(22例)CYP3A4表达水平为22.0(19.3-25.0)明显低于无反应者(14例为19.1(14.8-22.0);Z=-2.08,P=0.038]。本组乳腺癌手术患者CYP3A4*18变异频率过低[1/(76×2),0.66%],未能与CYP3A4表达水平和化疗反应进行关联分析。结论乳腺癌组织可表达CYP3A4,其表达水平的高低可能与基于紫杉类药物的化疗反应相关。
Objective To study CYP3A4 mRNA expression in breast cancer tissues and its correlations with chemotherapy responses,and explore the heredity base of CYP3A4 expression variation.Methods The study group included 40 cases with mastectomy,36 cases with neoadjuvant chemotherapy followed by surgery,and 200 cases with adjuvant chemotherapy for breast cancer.Taxanes-based regiment was administrated to the 36 neoadjuvant chemotherapy patients.CYP3A4 mRNA expression in cancer tissues and their adjacent breast tissues were assayed by real-time RT-PCR.CYP3A418 were genotyped by ligation-dependent SNP genotyping method.Results CYP3A4 mRNA were expressed at low to moderate levels in majority of cancer tissues and adjacent breast tissues.In 40 patients with surgery alone,CYP3A4 levels（ΔCt） were 21.8（18.7-24.2） and 21.3（18.0-23.1）,respectively,and in 36 patients with neoadjuvant chemotherapy,its levels were 20.7（16.2-24.7） and 21.1（17.0-23.8）,respectively（P0.05）.CYP3A4 mRNA levels of responders（n=22） for neoadjuvant chemotherapy were 22.0（19.3-25.0）,significantly lower than those of non-responders [n=14,19.1（14.8-22.0）;Z=-2.08,P=0.038].Because of low mutant frequency of CYP3A418 [1/（76×2）,0.66%] in 76 operative patients,further analyses were not done among CYP3A4 genotype,its expression or chemotherapy response.Conclusion CYP3A4 is expressed in breast cancer tissue,and its levels may predict the responses of taxanes-based chemotherapy.
出处
《中国实验诊断学》
北大核心
2010年第10期1554-1557,共4页
Chinese Journal of Laboratory Diagnosis
基金
江苏省社会发展科技计划项目(BS2007077)
国家自然科学基金资助项目(30840093)
