Abstract
PurposeBMI1, which is a major component of the polycomb group complex 1, is an essential epigenetic repressor of multiple regulatory genes and has been identified as a cancer stem cell (CSC) marker in several cancers. However, its role in breast cancer (BC) remains to be defined. In this study, we have evaluated the prognostic significance of BMI1 among the different molecular subtypes and assessed its association with other breast CSC markers (BCSC).Material and methodBMI1 copy number and mRNA was assessed in large and well-characterised cohorts of early-stage BC patients [METABRIC (n = 1980) and the Bc-GenExMiner (n = 9616) databases]. BMI1 protein expression was assessed using tissue microarray and immunohistochemistry in a cohort of 870 invasive BC patients with long-term outcome data and the expression of a panel of BCSC markers was monitored.ResultBMI1 expression, prognostic significance and its association with BCSC markers were differed between molecular classes. In the luminal oestrogen receptor-positive (ER+) BC, BMI1 showed significantly higher expression compared to ER− tumours. BMI1 showed positive correlation with favourable prognostic features and it was negatively associated with the expression of key BCSC markers (ALDH1A1, CD24, CD44, CD133, SOX10 and SOX9). High expression of BMI1 was associated with longer breast cancer-specific survival (BCSS) independent of other prognostic variables. In the basal triple negative BC subtype, BMI1 expression showed positive association with CD133 and SOX10 and it was significantly associated with shorter BCSS.ConclusionHigh BMI1 expression is associated with clinicopathological variables and outcome in BC. However, this association is dependent on the molecular subtypes. Further functional assessment to detect its underlying mechanistic roles in BC subtypes is warranted.
Highlights
Polycomb complex protein or B-lymphoma Moloney murine leukaemia virus insertion region-1 (BMI1) is a member of the polycomb family which are a group of transcriptional1 3 Vol.:(0123456789)Breast Cancer Research and Treatment (2020) 182:581–589 repressors [1, 2]
Arnes et al have reported that low expression of BMI1 is associated with high expression of Aldehyde dehydrogenase 1 (ALDH1) in African breast cancer (BC) patients, where ALDH1 has been used as a functional marker to define the breast cancer stem cells (BCSC) [11]
We further investigated the association of BMI1 expression and key BC stem cell (BCSC) biomarkers
Summary
Polycomb complex protein or B-lymphoma Moloney murine leukaemia virus insertion region-1 (BMI1) is a member of the polycomb family which are a group of transcriptional1 3 Vol.:(0123456789)Breast Cancer Research and Treatment (2020) 182:581–589 repressors [1, 2]. BMI1 has a RING finger at the N-terminus, a central helix-turn-helix domain and a carboxyl-terminal PEST-like domain at the C-terminal end. The RING domain is required for BMI1 to localise to DNA strand breaks; it is involved in DNA damage response. The central helix-turn-helix domain with RING domain increases the life span of the cell. BMI1 has been shown to behave as a key regulator in the self-renewal, differentiation and tumour initiation of breast cancer stem cells (BCSC) [8]. Conflicting data have been reported in the same study where high expression of BMI1 at mRNA and protein levels was associated with high expression of ER and positive axillary lymph node metastasis, leading to some difficulty in the interpretation of the results [14]
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