A six-gene signature predicting breast cancer lung metastasis
A six-gene signature predicting breast cancer lung metastasis
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DOI：
10.1158/0008-5472.can-08-0436
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发表时间：
2008-08-01
期刊：
影响因子：
11.2
通讯作者：
Driouch, Keltouma
中科院分区：
文献类型：
--
作者：
Landemaine, Thomas;Jackson, Amanda;Driouch, Keltouma
肺是转移性乳腺癌细胞的常见靶点，但潜在的分子机制尚不清楚。所有现有的数据都是使用原发性肿瘤中发现的基因表达测量值与临床结果之间的统计学关联或使用来自小鼠肿瘤模型的实验来源的签名获得的。在这里，我们描述了一种独特的方法，包括使用从肺转移灶手术切除的组织，并将它们的基因表达谱与来自非肺部位的基因表达谱进行比较，所有这些基因表达谱都来自乳腺癌患者。我们发现，器官特异性转移灶的基因表达谱可用于预测乳腺癌的肺转移。我们确定了一组21个肺转移相关基因。使用72例淋巴结阴性乳腺癌患者的队列，我们开发了一种6基因预后分类器，该分类器可区分具有显著较高肺转移风险的乳腺原发癌。然后，我们在由总共721名患者组成的3个独立的乳腺癌队列中验证了6个基因签名的预测能力。最后，我们表明，签名独立于已知的标准临床变量和先前建立的肺转移签名的基础上，实验性乳腺癌转移模型，提高了风险分层。
The lungs are a frequent target of metastatic breast cancer cells, but the underlying molecular mechanisms are unclear. All existing data were obtained either using statistical association between gene expression measurements found in primary tumors and clinical outcome, or using experimentally derived signatures from mouse tumor models. Here, we describe a distinct approach that consists of using tissue surgically resected from lung metastatic lesions and comparing their gene expression profiles with those from nonpulmonary sites, all coming from breast cancer patients. We show that the gene expression profiles of organ-specific metastatic lesions can be used to predict lung metastasis in breast cancer. We identified a set of 21 lung metastasisassociated genes. Using a cohort of 72 lymph node-negative breast cancer patients, we developed a 6-gene prognostic classifier that discriminated breast primary cancers with a significantly higher risk of lung metastasis. We then validated the predictive ability of the 6-gene signature in 3 independent cohorts of breast cancers consisting of a total of 721 patients. Finally, we show that the signature improves risk stratification independently of known standard clinical variables and a previously established lung metastasis signature based on an experimental breast cancer metastasis model.