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Heparanase: a potential marker of worse prognosis in estrogen receptor-positive breast cancer

par Zahavi, Tamar;Salmon-Divon, Mali;Salgado, Roberto;Elkin, Michael;Hermano, Esther;Rubinstein, Ariel A.M.;Francis, Prudence P.A.;Di Leo, A.;Viale, Giuseppe;de Azambuja, Evandro ;Ameye, Lieveke;Sotiriou, Christos ;Salmon, Asher;Kravchenko-Balasha, Nataly;Sonnenblick, Amir
Référence NPJ breast cancer, 7, 1, 67
Publication Publié, 2021-12

Article révisé par les pairs

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Résumé :

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.