A six-gene signature predicting breast cancer lung metastasis

作者：Landemaine Thomas; Jackson Amanda; Bellahcene Akeila; Rucci Nadia; Sin Soraya; Martin Abad Berta; Sierra Angels; Boudinet Alain; Guinebretiere Jean Marc; Ricevuto Enrico; Nogues Catherine; Briffod Marianne; Bieche Ivan; Cherel Pascal; Garcia Teresa; Castronovo Vincent; Teti Anna; Lidereau Rosette; Driouch Keltouma^*

来源：Cancer Research, 2008, 68(15): 6092-6099.

DOI：10.1158/0008-5472.CAN-08-0436

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.

• 出版日期2008-8-1