Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target
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 targ...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/16/3918 |
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| author | Malvina Koni Isabella Castellano Emilio Venturelli Alessandro Sarcinella Tatiana Lopatina Cristina Grange Massimo Cedrino Saveria Femminò Paolo Cossu-Rocca Sandra Orrù Fabrizio D’Ascenzo Ilaria Cotellessa Cristian Tampieri Carla Debernardi Giovanni Cugliari Giuseppe Matullo Giovanni Camussi Maria Rosaria De Miglio Maria Felice Brizzi |
| author_facet | Malvina Koni Isabella Castellano Emilio Venturelli Alessandro Sarcinella Tatiana Lopatina Cristina Grange Massimo Cedrino Saveria Femminò Paolo Cossu-Rocca Sandra Orrù Fabrizio D’Ascenzo Ilaria Cotellessa Cristian Tampieri Carla Debernardi Giovanni Cugliari Giuseppe Matullo Giovanni Camussi Maria Rosaria De Miglio Maria Felice Brizzi |
| author_sort | Malvina Koni |
| collection | DOAJ |
| description | 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 (<i>p</i> = 0.026) and poor overall survival (hazard ratio = 1.50; 95% CI = 1.01–2.2; <i>p</i> = 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 (<i>p</i> = 0.017, <i>p</i>adj = 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. |
| first_indexed | 2024-03-09T13:43:46Z |
| format | Article |
| id | doaj.art-ec4e40448fbf4927ad47f747dc15d49a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:43:46Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ec4e40448fbf4927ad47f747dc15d49a2023-11-30T21:04:09ZengMDPI AGCancers2072-66942022-08-011416391810.3390/cancers14163918Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic TargetMalvina Koni0Isabella Castellano1Emilio Venturelli2Alessandro Sarcinella3Tatiana Lopatina4Cristina Grange5Massimo Cedrino6Saveria Femminò7Paolo Cossu-Rocca8Sandra Orrù9Fabrizio D’Ascenzo10Ilaria Cotellessa11Cristian Tampieri12Carla Debernardi13Giovanni Cugliari14Giuseppe Matullo15Giovanni Camussi16Maria Rosaria De Miglio17Maria Felice Brizzi18Department of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyAnatomic Pathology Unit, Department of Diagnostic Services, “Giovanni Paolo II” Hospital, ASL Gallura, 07026 Olbia, ItalyDepartment of Pathology, “A. Businco” Oncologic Hospital, ARNAS Brotzu, 09121 Cagliari, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyTumour 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 (<i>p</i> = 0.026) and poor overall survival (hazard ratio = 1.50; 95% CI = 1.01–2.2; <i>p</i> = 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 (<i>p</i> = 0.017, <i>p</i>adj = 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.https://www.mdpi.com/2072-6694/14/16/3918interleukin-3/interleukin-3 receptor αtriple-negative breast cancervascular mimicryprogrammed cell death-ligand 1 |
| spellingShingle | Malvina Koni Isabella Castellano Emilio Venturelli Alessandro Sarcinella Tatiana Lopatina Cristina Grange Massimo Cedrino Saveria Femminò Paolo Cossu-Rocca Sandra Orrù Fabrizio D’Ascenzo Ilaria Cotellessa Cristian Tampieri Carla Debernardi Giovanni Cugliari Giuseppe Matullo Giovanni Camussi Maria Rosaria De Miglio Maria Felice Brizzi Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target Cancers interleukin-3/interleukin-3 receptor α triple-negative breast cancer vascular mimicry programmed cell death-ligand 1 |
| title | Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target |
| title_full | Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target |
| title_fullStr | Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target |
| title_full_unstemmed | Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target |
| title_short | Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target |
| title_sort | interleukin 3 receptor α in triple negative breast cancer tnbc an additional novel biomarker of tnbc aggressiveness and a therapeutic target |
| topic | interleukin-3/interleukin-3 receptor α triple-negative breast cancer vascular mimicry programmed cell death-ligand 1 |
| url | https://www.mdpi.com/2072-6694/14/16/3918 |
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