title: Galectin signatures contribute to the heterogeneity of breast cancer and provide new prognostic information and therapeutic targets.
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.
authors.affiliation: INRS-Institut Armand-Frappier, Laval, Quebec H7V 1B7, Canada.|IRIC | Université de Montréal, Montreal, Quebec H3T 1J4, Canada.
authors.forename: Andrée-Anne
authors.initials: AA
authors.lastname: Grosset
authors.affiliation: INRS-Institut Armand-Frappier, Laval, Quebec H7V 1B7, Canada.
authors.forename: Marilyne
authors.initials: M
authors.lastname: Labrie
authors.affiliation: INRS-Institut Armand-Frappier, Laval, Quebec H7V 1B7, Canada.
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Vladoiu
authors.affiliation: IRIC | Université de Montréal, Montreal, Quebec H3T 1J4, Canada.
authors.forename: Einas M
authors.initials: EM
authors.lastname: Yousef
authors.affiliation: IRIC | Université de Montréal, Montreal, Quebec H3T 1J4, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Gaboury
authors.affiliation: INRS-Institut Armand-Frappier, Laval, Quebec H7V 1B7, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: St-Pierre
mesh_terms: D001798:Blood Proteins; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D037161:Galectins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D064726:Triple Negative Breast Neoplasms / Q000401:mortality* / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D001798:Blood Proteins; D037483:Galectin 1; D037502:Galectin 3; D037161:Galectins; C445499:LGALS1 protein, human; C428445:LGALS3 protein, human; C091991:LGALS8 protein, human; C105032:LGALS9 protein, human
keywords: breast cancer; galectins; immunohistochemistry; tissue microarrays; triple negative