Integrated Analysis of Key Differentially Expressed Genes Identifies DBN1 as a Predictive Marker of Response to Endocrine Therapy in Luminal Breast Cancer
| Autor: | Lutfi Alfarsi, Emad A. Rakha, Ian O. Ellis, Omar J. Mohammed, Brendah K. Masisi, Ruth M. Parks, Andrew R. Green, Rokaya El Ansari |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty medicine.medical_treatment lcsh:RC254-282 Article endocrine resistance 03 medical and health sciences 0302 clinical medicine Breast cancer breast cancer Internal medicine Endocrine system Medicine Stage (cooking) DBN1 predictive biomarker Predictive marker business.industry Endocrine therapy lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease oestrogen receptor 030104 developmental biology Differentially expressed genes 030220 oncology & carcinogenesis business Adjuvant Hormone |
| Zdroj: | Cancers Volume 12 Issue 6 Cancers, Vol 12, Iss 1549, p 1549 (2020) |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers12061549 |
| Popis: | Endocrine therapy is the mainstay of adjuvant treatment for patients with luminal breast cancer. Despite ongoing advances in endocrine therapy to date, a proportion of patients ultimately develop endocrine resistance, resulting in failure of therapy and poor prognosis. Therefore, as part of the growing concept of personalised medicine, the need for identification of predictive markers of endocrine therapy response at an early stage, is recognised. The METABRIC series was used to identify differentially expressed genes (DEGs) in term of response to adjuvant endocrine therapy. Drebrin 1 (DBN1) was identified as a key DEG associated with response to hormone treatment. Next, large, well-characterised cohorts of primary luminal breast cancer with long-term follow-up were assessed at the mRNA and protein levels for the value of DBN1 as a prognostic marker in luminal breast cancer, as well as its potential for predicting the benefit of endocrine therapy. DBN1 positivity was associated with aggressive clinicopathological variables and poor patient outcomes. Importantly, high DBN1 expression predicted relapse patients who were subject to adjuvant endocrine treatment. Our results further demonstrate that DBN1 is an independent prognostic marker in luminal breast cancer. Its association with the response to endocrine therapy and outcome provides evidence for DBN1 as a potential biomarker in luminal breast cancer, particularly for the benefit of endocrine treatment. Further functional investigations into the mechanisms underlying sensitivity to endocrine therapy is required. |
| Databáze: | OpenAIRE |
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