Global gene expression changes during neoadjuvant chemotherapy for human breast cancer
Global gene expression changes during neoadjuvant chemotherapy for human breast cancer
复制标题
DOI：
10.1097/00130404-200211000-00010
复制
发表时间：
2002-11-01
期刊：
影响因子：
2.2
通讯作者：
Pusztai, L
中科院分区：
文献类型：
--
作者：
Buchholz, TA;Stivers, DN;Pusztai, L
本研究的目的是分析全球基因表达的变化，在新辅助化疗原发性乳腺cancer.PATIENTS和METHODSSCore肿瘤活检标本的系列肿瘤核心活检标本治疗前和治疗后24和/或48小时从21名妇女谁是开始化疗乳腺癌。提取RNA，并合成放射性标记的互补DNA。将互补DNA探针与含有超过25，000个人类序列克隆的高密度微阵列膜杂交。结果56份可用核心样本中有25份（45%）产生了足够数量和质量的RNA用于微阵列分析。微阵列配置文件进行了治疗前和治疗后标本的患者的样本，导致连续数据集为5名患者（14个标本）。来自个体患者的系列样品比取自不同患者的样品更紧密地聚集。个体基因表达的方差分析显示，与不同肿瘤的预处理样品（平均732个基因）相比，在不同时间个体肿瘤中具有5倍表达差异的基因显著较少（平均359个基因）。对治疗有良好病理反应的患者的基因模式与那些反应差的患者明显不同。在治疗期间，所有患者均发生了显著的转录应答。令人惊讶的是，所有患者化疗后有不同的基因变化，没有一个单一的基因有一个显着的表达变化，在所有五个patients. CumulationThis是第一个报告，显示全球基因表达变化化疗期间在人类实体瘤。超过25，000个基因的综合基因表达谱可以从核心活检标本中获得。一个显着的多样性，在转录反应中观察到个别情况。需要进一步的数据来确定基因谱是否可以预测对化疗的反应。
PURPOSEThe purpose of this study was to analyze global gene expression changes in serial tumor core biopsy specimens taken during neoadjuvant chemotherapy for primary breast cancer.PATIENTS AND METHODSCore biopsy specimens from tumors were obtained before treatment and 24 and/or 48 hours after treatment from 21 women who were beginning chemotherapy for breast cancer. RNA was extracted, and radiolabeled complementary DNA was synthesized. The complementary DNA probes were hybridized to high-density microarray membranes that contained more than 25,000 human sequence clones. Hierarchical cluster analysis was used to compare the degree of similarity between expression profiles.RESULTSTwenty-five (45%) of the 56 available core specimens yielded sufficient quantity and quality RNA for microarray analysis. Microarray profiles were performed only on samples from patients with pretreatment and posttreatment specimens, resulting in serial data sets for five patients (14 specimens). The serial samples from individual patients clustered more closely than the samples taken from different patients. Analyses of the variance of individual gene expression showed that there were significantly fewer genes with fivefold differences in expression in an individual tumor at different times (average, 359 genes) versus pretreatment samples of different tumors (average, 732 genes). Patients with a good pathological response to treatment had gene patterns that clustered distinctly from those of poor responders. Significant transcriptional response occurred in all patients during therapy. Surprisingly, all patients had different genes change after chemotherapy, with no single gene having a significant expression change in all five patients.DISCUSSIONThis is the first report to show global gene expression changes during chemotherapy in a human solid tumor. Comprehensive gene expression profiles of more than 25,000 genes can be obtained from core biopsy specimens. A remarkable diversity, in transcriptional response was observed for individual cases. Further data are needed to determine whether gene profiling can predict response to chemotherapy.