Utility of ankyrin 3 as a prognostic marker in androgen-receptor-positive breast cancer

• Published in: Breast cancer research and treatment Vol. 176; no. 1; pp. 63 - 73
• Main Authors: Kurozumi, Sasagu, Joseph, Chitra, Raafat, Sara, Sonbul, Sultan, Kariri, Yousif, Alsaeed, Sami, Pigera, Marian, Alsaleem, Mansour, Nolan, Christopher C., Johnston, Simon J., Aleskandarany, Mohammed A., Ogden, Angela, Fujii, Takaaki, Shirabe, Ken, Martin, Stewart G., Alshankyty, Ibraheem, Mongan, Nigel P., Ellis, Ian O., Green, Andrew R., Rakha, Emad A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-07-2019; Springer; Springer Nature B.V
• Subjects: Androgen receptors; Androgens; Ankyrins; Breast cancer; Cancer; Cancer research; Epidermal growth factor; ErbB-2 protein; Estrogen; Gene expression; Genes; Genetic aspects; Genomes; Genomics; Immunohistochemistry; Medical colleges; Medicine; Medicine & Public Health; Oncology; Oncology, Experimental; Patients; Preclinical Study; Progesterone; Prognosis; Protein expression; Proteins; Proteomics; RNA; Signal transduction; Taxonomy; Tumors; Invasive breast cancer; Ankyrin 3; Prognostic marker; Androgen receptor
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-019-05216-w

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.