Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
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DOI：
10.1073/pnas.191367098
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发表时间：
2001-09-11
影响因子：
11.1
通讯作者：
Borresen-Dale, AL
中科院分区：
文献类型：
--
作者：
Sorlie, T;Perou, CM;Borresen-Dale, AL
本研究的目的是根据 cDNA 微阵列基因表达模式的变化对乳腺癌进行分类，并将肿瘤特征与临床结果相关联。通过层次聚类分析了代表 78 种癌症、三种纤维腺瘤和四种正常乳腺组织的总共 85 个 cDNA 微阵列实验。正如之前报道的，根据基因表达的变化，癌症可以分为基底上皮样组、ERBB2过表达组和正常乳腺样组。一项新的发现是，先前表征的管腔上皮/雌激素受体阳性组可以分为至少两个亚组，每个亚组具有独特的表达谱。通过使用两个不同的基因集进行聚类，这些亚型被证明是相当稳健的：第一个是先前选择的一组 456 个 cDNA 克隆，用于反映肿瘤的内在特性，第二个是与患者结果高度相关的基因集。在一项前瞻性研究中，对接受统一治疗的局部晚期乳腺癌患者亚组进行的生存分析显示，属于不同组的患者的结局存在显着差异，包括基底样亚型的预后不良以及两个雌激素受体阳性组的结局存在显着差异。
The purpose of this study was to classify breast carcinomas based on variations in gene expression patterns derived from cDNA microarrays and to correlate tumor characteristics to clinical outcome. A total of 85 cDNA microarray experiments representing 78 cancers, three fibroadenomas, and four normal breast tissues were analyzed by hierarchical clustering. As reported previously, the cancers could be classified into a basal epithelial-like group, an ERBB2-overexpressing group and a normal breast-like group based on variations in gene expression. A novel finding was that the previously characterized luminal epithelial/estrogen receptor-positive group could be divided into at least two subgroups, each with a distinctive expression profile. These subtypes proved to be reasonably robust by clustering using two different gene sets: first, a set of 456 cDNA clones previously selected to reflect intrinsic properties of the tumors and, second, a gene set that highly correlated with patient outcome. Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.