[en] 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 metastasis-associated 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.
Bellahcene, Akeila ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Rucci, Nadia
Sin, Soraya
Abad, Berta Martin
Sierra, Angels
Boudinet, Alain
Guinebretiere, Jean-Marc
Ricevuto, Enrico
Nogues, Catherine
Briffod, Marianne
Bieche, Ivan
Cherel, Pascal
Garcia, Teresa
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire - GIGA-R : Labo de recherche sur les métastases
A six-gene signature predicting breast cancer lung metastasis.
Publication date :
2008
Journal title :
Cancer Research
ISSN :
0008-5472
eISSN :
1538-7445
Publisher :
American Association for Cancer Research, Inc. (AACR), Baltimore, United States - Maryland
Volume :
68
Issue :
15
Pages :
6092-9
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
European Commission FPVI METABRE (LSHC-CT-2004-503049) La Ligue contre le cander des Hauts de Seine European Community withe the METABRE consortium BCRF - Breast Cancer Research Foundation F.R.S.-FNRS - Fonds de la Recherche Scientifique
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