Oncotarget

Research Papers:

Galectin signatures contribute to the heterogeneity of breast cancer and provide new prognostic information and therapeutic targets

Andrée-Anne Grosset, Marilyne Labrie, Maria Claudia Vladoiu, Einas M Yousef, Louis Gaboury and Yves St-Pierre _

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Oncotarget. 2016; 7:18183-18203. https://doi.org/10.18632/oncotarget.7784

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Abstract

Andrée-Anne Grosset1,2, Marilyne Labrie1, Maria Claudia Vladoiu1, Einas M Yousef2, Louis Gaboury2, Yves St-Pierre1

1INRS-Institut Armand-Frappier, Laval, Quebec H7V 1B7, Canada

2IRIC | Université de Montréal, Montreal, Quebec H3T 1J4, Canada

Correspondence to:

Yves St-Pierre, e-mail: yves.st-pierre@iaf.inrs.ca

Keywords: breast cancer, triple negative, galectins, tissue microarrays, immunohistochemistry

Received: November 05, 2015     Accepted: January 29, 2016     Published: February 27, 2016

ABSTRACT

Because of their ability to induce local immunosuppression and to confer cancer cells with resistance to apoptosis, members of the galectin family are emerging as a new class of actionable targets in cancer. Unfortunately, we have yet to obtain a clear picture of the galectin signatures in cancer cells and the surrounding tumor microenvironment. The aim of this study was to provide the first detailed analysis of the galectin signature in molecular subtypes of breast cancer. Expression signatures of galectins were obtained at the mRNA and protein levels. A particular attention was paid to stromal versus epithelial staining and to subcellular compartmentalization. Analysis of the stromal signature showed that gal-1, -3, -9-positive stroma were preferentially found in triple-negative (TN) and HER2 subtypes. In cancer cells, gal-1, -3, -8, and -9 showed a dual expression pattern, being found either in the cytosol or in the cytosol and the nucleus. TN patients with gal-8-positive nuclei had significantly better disease-free survival (DFS), distant-disease-free survival (DDFS), and overall survival (OS). In contrast, high expression of nuclear gal-1 correlated with poor DDFS and OS. TNBC patients who were positive for both nuclear gal-1 and gal-8 had 5-year DFS and DDFS of 100%, suggesting a dominance of the gal-8 phenotype. Overall, the results indicate that specific galectin expression signatures contribute to the phenotypic heterogeneity of aggressive subtypes of breast cancer. Our data also suggest that galectins have clinical utility as indicators of disease progression and therapeutic targets in aggressive molecular subtypes of breast cancer.


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