Gene expression profiles derived from fine needle aspiration correlate with response to systemic chemotherapy in breast cancer.
Gene expression profiles derived from fine needle aspiration correlate with response to systemic chemotherapy in breast cancer.
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DOI：
10.1186/bcr433
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发表时间：
2002
影响因子：
7.4
通讯作者：
Liu, Edison T
中科院分区：
文献类型：
--
作者：
Sotiriou, Christos;Powles, Trevor J;Dowsett, Mitch;Jazaeri, Amir A;Feldman, Andrew L;Assersohn, Laura;Gadisetti, Chandramouli;Libutti, Steven K;Liu, Edison T
乳腺癌的耐药性是化疗成功的主要障碍。在这项研究中，我们使用基因芯片技术来检测系统化疗前后的乳腺肿瘤细针抽吸(FNA)获得的基因表达谱。我们的目标是确定从有限数量的组织中获得具有代表性的表达阵列图谱的可行性，并识别那些与治疗反应相关的表达图谱。重复的术前FNA样本取自6名将要接受初次手术治疗的患者。此外，10例接受新辅助化疗的患者在化疗前接受了两次FNA(阿霉素60 mg/m2和环磷酰胺600 mg/m2)，然后在第一周期结束后第21天再次进行FNA。用T7 Eberwin‘s程序扩增总RNA，将标记的cDNA杂交到7600个特征的玻璃基因芯片上。我们确定了候选基因表达谱，这些基因表达谱可能会区分对化疗完全有效的肿瘤和没有反应的肿瘤，并发现在一个周期的化疗后，有反应组的基因数量是无反应组的10倍。这项研究支持FNA衍生的乳腺癌基因芯片表达谱作为研究耐药机制的一种综合基因组方法的适用性。我们的发现还证明了监测化疗后表达谱变化作为药效学效应的衡量标准的潜力，并表明当经过更大规模的研究验证时，这些方法可能会产生有用的结果。
Drug resistance in breast cancer is a major obstacle to successful chemotherapy. In this study we used cDNA microarray technology to examine gene expression profiles obtained from fine needle aspiration (FNA) of primary breast tumors before and after systemic chemotherapy. Our goal was to determine the feasibility of obtaining representative expression array profiles from limited amounts of tissue and to identify those expression profiles that correlate with treatment response. Repeat presurgical FNA samples were taken from six patients who were to undergo primary surgical treatment. Additionally, a group of 10 patients who were to receive neoadjuvant chemotherapy underwent two FNAs before chemotherapy (adriamycin 60 mg/m2 and cyclophosphamide 600 mg/m2) followed by another FNA on day 21 after the first cycle. Total RNA was amplified with T7 Eberwine's procedure and labeled cDNA was hybridized onto a 7600-feature glass cDNA microarray. We identified candidate gene expression profiles that might distinguish tumors with complete response to chemotherapy from tumors that do not respond, and found that the number of genes that change after one cycle of chemotherapy was 10 times greater in the responding group than in the non-responding group. This study supports the suitability of FNA-derived cDNA microarray expression profiling of breast cancers as a comprehensive genomic approach for studying the mechanisms of drug resistance. Our findings also demonstrate the potential of monitoring post-chemotherapy changes in expression profiles as a measure of pharmacodynamic effect and suggests that these approaches might yield useful results when validated by larger studies.