Sasagu Kurozumi1,2, Chitra Joseph1, Sara Raafat1,3, Sultan Sonbul1, Yousif Kariri1, Sami Alsaeed1, Marian Pigera1, Mansour Alsaleem1, Christopher C Nolan1, Simon J Johnston1, Mohammed A Aleskandarany1,4, Angela Ogden1, Takaaki Fujii2, Ken Shirabe2, Stewart G Martin1, Ibraheem Alshankyty5, Nigel P Mongan6,7, Ian O Ellis1, Andrew R Green1, Emad A Rakha8,9,10. 1. Division of Cancer and Stem Cells, Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham, UK. 2. Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan. 3. Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 4. Faculty of Medicine, Menoufyia University, Shebin El Kom, Egypt. 5. Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. 6. Cancer Biology and Translational Research, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK. 7. Department of Pharmacology, Weill Cornell Medicine, New York, USA. 8. Division of Cancer and Stem Cells, Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham, UK. emad.rakha@nottingham.ac.uk. 9. Faculty of Medicine, Menoufyia University, Shebin El Kom, Egypt. emad.rakha@nottingham.ac.uk. 10. Division of Cancer and Stem Cells, Department of Histopathology, School of Medicine, The University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, NG5 1PB, UK. emad.rakha@nottingham.ac.uk.
Abstract
PURPOSE: Androgen receptor (AR) and AR signaling pathways are thought to play a role in breast cancer (BC) and are potentially related to treatment responses and outcomes. Ankyrin 3 (ANK3) is associated with AR stability in cancer cells. In the present study, we investigated the clinicopathological utility of ANK3 expression with emphasis on AR and its associated signalling pathway at transcriptomic and proteomic phases. PATIENTS AND METHODS: The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (n = 1980) and The Cancer Genome Atlas (TCGA) dataset (n = 1039) were used to assess the expression and significance of ANK3 mRNA and other AR signalling pathway-associated gene signature. Using immunohistochemistry, ANK3 protein expression was evaluated in large (n = 982) cohort of early-stage BC with long-term follow-up and compared with clinicopathological characteristics and its prognostic value in the whole cohort and the subgroups stratified by AR protein expression. RESULTS: An AR-related gene signature was developed, comprising 20 genes, which included ANK3. This AR-related gene signature was significantly associated with AR mRNA expression, oestrogen receptor, human epidermal growth factor receptor 2 (HER2) status and the patients' outcomes. In tumours with high AR protein expression (n = 614), high ANK3 protein expression was significantly associated with progesterone receptor positivity and it was independently associated with the good outcomes (p = 0.025). CONCLUSIONS: This study indicates that ANK3 is related to AR signalling pathway and is associated with BC prognosis.
PURPOSE:Androgen receptor (AR) and AR signaling pathways are thought to play a role in breast cancer (BC) and are potentially related to treatment responses and outcomes. Ankyrin 3 (ANK3) is associated with AR stability in cancer cells. In the present study, we investigated the clinicopathological utility of ANK3 expression with emphasis on AR and its associated signalling pathway at transcriptomic and proteomic phases. PATIENTS AND METHODS: The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (n = 1980) and The Cancer Genome Atlas (TCGA) dataset (n = 1039) were used to assess the expression and significance of ANK3 mRNA and other AR signalling pathway-associated gene signature. Using immunohistochemistry, ANK3 protein expression was evaluated in large (n = 982) cohort of early-stage BC with long-term follow-up and compared with clinicopathological characteristics and its prognostic value in the whole cohort and the subgroups stratified by AR protein expression. RESULTS: An AR-related gene signature was developed, comprising 20 genes, which included ANK3. This AR-related gene signature was significantly associated with AR mRNA expression, oestrogen receptor, humanepidermal growth factor receptor 2 (HER2) status and the patients' outcomes. In tumours with high AR protein expression (n = 614), high ANK3 protein expression was significantly associated with progesterone receptor positivity and it was independently associated with the good outcomes (p = 0.025). CONCLUSIONS: This study indicates that ANK3 is related to AR signalling pathway and is associated with BC prognosis.
Entities:
Keywords:
Androgen receptor; Ankyrin 3; Invasive breast cancer; Prognostic marker