Article abstract
Nature Medicine 14, 518 - 527 (2008)
Published online: 27 April 2008 | doi:10.1038/nm1764
Stromal gene expression predicts clinical outcome in breast cancer
Greg Finak1,2,3, Nicholas Bertos2,7, Francois Pepin1,2,3,7, Svetlana Sadekova2, Margarita Souleimanova2, Hong Zhao2, Haiying Chen2, Gulbeyaz Omeroglu2, Sarkis Meterissian4, Atilla Omeroglu6, Michael Hallett1,3 & Morag Park2,3,5
Abstract
Although it is increasingly evident that cancer is influenced by signals emanating from tumor stroma, little is known regarding how changes in stromal gene expression affect epithelial tumor progression. We used laser capture microdissection to compare gene expression profiles of tumor stroma from 53 primary breast tumors and derived signatures strongly associated with clinical outcome. We present a new stroma-derived prognostic predictor (SDPP) that stratifies disease outcome independently of standard clinical prognostic factors and published expression-based predictors. The SDPP predicts outcome in several published whole tumor–derived expression data sets, identifies poor-outcome individuals from multiple clinical subtypes, including lymph node–negative tumors, and shows increased accuracy with respect to previously published predictors, especially for HER2-positive tumors. Prognostic power increases substantially when the predictor is combined with existing outcome predictors. Genes represented in the SDPP reveal the strong prognostic capacity of differential immune responses as well as angiogenic and hypoxic responses, highlighting the importance of stromal biology in tumor progression.
- McGill Centre for Bioinformatics, 3775 University Street, McGill University, Québec H3A 2B4, Canada.
- Molecular Oncology Group, 687 Pine Avenue West, McGill University Health Centre, Québec H3A 1A1, Canada.
- Department of Biochemistry, 3655 Promenade Sir William Osler, McGill University, Québec H3G 1Y6, Canada.
- Department of Surgery, 687 Pine Avenue West, McGill University, Québec H3A 1A1, Canada.
- Department of Oncology, 687 Pine Avenue West, McGill University, Québec H3A 1A1, Canada.
- Department of Pathology, 3775 University Street, McGill University, Québec, H3A 2B4, Canada.
- These authors contributed equally to this work.
Correspondence to: Morag Park2,3,5 e-mail: morag.park@mcgill.ca
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