Heparanase promotes tumor growth in breast tumors. We now evaluated heparanase protein and gene-expression status and investigated its impact on disease-free survival in order to gain better insight into the role of heparanase in ER-positive (ER+) breast cancer prognosis and to clarify its role in cell survival following chemotherapy. Using pooled analysis of gene-expression data, we found that heparanase was associated with a worse prognosis in estrogen receptor-positive (ER+) tumors (log-rank p < 10-10) and predictive to chemotherapy resistance (interaction p = 0.0001) but not hormonal therapy (Interaction p = 0.62). These results were confirmed by analysis of data from a phase III, prospective randomized trial which showed that heparanase protein expression is associated with increased risk of recurrence in ER+ breast tumors (log-rank p = 0.004). In vitro experiments showed that heparanase promoted tumor progression and increased cell viability via epithelial-mesenchymal transition, stemness, and anti-apoptosis pathways in luminal breast cancer. Taken together, our results demonstrated that heparanase is associated with worse outcomes and increased cell viability in ER+ BC.
Heparanase: a potential marker of worse prognosis in estrogen receptor-positive breast cancer / T. Zahavi, M. Salmon-Divon, R. Salgado, M. Elkin, E. Hermano, A.M. Rubinstein, P.A. Francis, A. Di Leo, G. Viale, E. de Azambuja, L. Ameye, C. Sotiriou, A. Salmon, N. Kravchenko-Balasha, A. Sonnenblick. - In: NPJ BREAST CANCER. - ISSN 2374-4677. - 7:1(2021 May 28), pp. 67.1-67.9. [10.1038/s41523-021-00277-x]
|Titolo:||Heparanase: a potential marker of worse prognosis in estrogen receptor-positive breast cancer|
|Settore Scientifico Disciplinare:||Settore MED/08 - Anatomia Patologica|
|Data di pubblicazione:||28-mag-2021|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/s41523-021-00277-x|
|Appare nelle tipologie:||01 - Articolo su periodico|