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.
Highlights
Gene profiling studies have greatly helped at better classifying breast cancer into at least four generally recognized molecular subtypes
We first used the prognostic module of the Breast Cancer Gene-Expression Miner v3.1 public database to investigate galectin expression at the mRNA level among breast cancer molecular subtypes
We found that the relative expression of galectins among the different molecular subtype had a similar distribution, the percentage of patients with the highest expression of lgals8, and to a lesser extent lgals3, were lower in patients with a basal-like subtype (Figure 1B)
Summary
Gene profiling studies have greatly helped at better classifying breast cancer into at least four generally recognized molecular subtypes These molecular subtypes are identified based on the immunohistochemical expression of the estrogen (ER) and progesterone (PR) receptors and of Human Epidermal Growth Factor Receptor 2 (HER2), a member of the epidermal growth factor receptor family. These molecular subtypes include luminal A and B, HER2-positive, and triple negative breast cancer (TNBC; ER-, PR-, and HER2-negative tumor) [1, 2]. Such challenge is further complicated by the complexity of the tumor microenvironment (TME) which plays a critical role in the disease progression [5]
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