Tumour molecular annotation is mandatory for biomarker discovery and personalised approaches, particularly in triple-negative breast cancer (TNBC) lacking effective treatment options. In this study, the interleukin-3 receptor α (IL-3Rα) was investigated as a prognostic biomarker and therapeutic target in TNBC. IL-3Rα expression and patients' clinical and pathological features were retrospectively analysed in 421 TNBC patients. IL-3Rα was expressed in 69% human TNBC samples, and its expression was associated with nodal metastases (p = 0.026) and poor overall survival (hazard ratio = 1.50; 95% CI = 1.01-2.2; p = 0.04). The bioinformatics analysis on the Breast Invasive Carcinoma dataset of The Cancer Genome Atlas (TCGA) proved that IL-3Rα was highly expressed in TNBC compared with luminal breast cancers (p = 0.017, padj = 0.026). Functional studies demonstrated that IL-3Rα activation induced epithelial-to-endothelial and epithelial-to-mesenchymal transition, promoted large blood lacunae and lung metastasis formation, and increased programmed-cell death ligand-1 (PD-L1) in primary tumours and metastases. Based on the TCGA data, IL-3Rα, PD-L1, and EMT coding genes were proposed to discriminate against TNBC aggressiveness (AUC = 0.86 95% CI = 0.82-0.89). Overall, this study identified IL-3Rα as an additional novel biomarker of TNBC aggressiveness and provided the rationale to further investigate its relevance as a therapeutic target.

Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target / Koni, Malvina; Castellano, Isabella; Venturelli, Emilio; Sarcinella, Alessandro; Lopatina, Tatiana; Grange, Cristina; Cedrino, Massimo; Femminò, Saveria; Paolo, Cossu-Rocca; Orrù, Sandra; D'Ascenzo, Fabrizio; Cotellessa, Ilaria; Tampieri, Cristian; Debernardi, Carla; Cugliari, Giovanni; Matullo, Giuseppe; Camussi, Giovanni; DE MIGLIO, Maria Rosaria; Felice Brizzi, Maria. - In: CANCERS. - ISSN 2072-6694. - 14:16(2022), p. 3918. [10.3390/cancers14163918]

Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target

Paolo Cossu-Rocca;Maria Rosaria De Miglio;
2022-01-01

Abstract

Tumour molecular annotation is mandatory for biomarker discovery and personalised approaches, particularly in triple-negative breast cancer (TNBC) lacking effective treatment options. In this study, the interleukin-3 receptor α (IL-3Rα) was investigated as a prognostic biomarker and therapeutic target in TNBC. IL-3Rα expression and patients' clinical and pathological features were retrospectively analysed in 421 TNBC patients. IL-3Rα was expressed in 69% human TNBC samples, and its expression was associated with nodal metastases (p = 0.026) and poor overall survival (hazard ratio = 1.50; 95% CI = 1.01-2.2; p = 0.04). The bioinformatics analysis on the Breast Invasive Carcinoma dataset of The Cancer Genome Atlas (TCGA) proved that IL-3Rα was highly expressed in TNBC compared with luminal breast cancers (p = 0.017, padj = 0.026). Functional studies demonstrated that IL-3Rα activation induced epithelial-to-endothelial and epithelial-to-mesenchymal transition, promoted large blood lacunae and lung metastasis formation, and increased programmed-cell death ligand-1 (PD-L1) in primary tumours and metastases. Based on the TCGA data, IL-3Rα, PD-L1, and EMT coding genes were proposed to discriminate against TNBC aggressiveness (AUC = 0.86 95% CI = 0.82-0.89). Overall, this study identified IL-3Rα as an additional novel biomarker of TNBC aggressiveness and provided the rationale to further investigate its relevance as a therapeutic target.
2022
Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target / Koni, Malvina; Castellano, Isabella; Venturelli, Emilio; Sarcinella, Alessandro; Lopatina, Tatiana; Grange, Cristina; Cedrino, Massimo; Femminò, Saveria; Paolo, Cossu-Rocca; Orrù, Sandra; D'Ascenzo, Fabrizio; Cotellessa, Ilaria; Tampieri, Cristian; Debernardi, Carla; Cugliari, Giovanni; Matullo, Giuseppe; Camussi, Giovanni; DE MIGLIO, Maria Rosaria; Felice Brizzi, Maria. - In: CANCERS. - ISSN 2072-6694. - 14:16(2022), p. 3918. [10.3390/cancers14163918]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/302946
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