The prognostic significance of BMI1 expression in invasive breast cancer is dependent on its molecular subtypes

Althobiti, Maryam; Muftah, Abir A; Aleskandarany, Mohammed A; Joseph, Chitra; Toss, Michael S; Green, Andrew; Rakha, Emad

Abstract

Purpose: BMI-1, 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 BMI-1 among the different molecular subtypes and assessed its association with other breast CSC markers (BCSC).
Material and Method: BMI-1 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]. BMI-1 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.
Result: BMI-1 expression, prognostic significance and its association with BCSC markers were differed between molecular classes. In the luminal oestrogen receptor positive (ER+) BC, BMI-1 showed significantly higher expression compared to ER- tumours. BMI-1 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 BMI-1 was associated with longer breast cancer specific survival (BCSS) independent of other prognostic variables. In the basal triple negative BC subtype, BMI-1 expression showed positive association with CD133 and SOX10 and it was significantly associated with shorter BCSS.
Conclusion: High 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.

Citation

Althobiti, M., Muftah, A. A., Aleskandarany, M. A., Joseph, C., Toss, M. S., Green, A., & Rakha, E. (2020). The prognostic significance of BMI1 expression in invasive breast cancer is dependent on its molecular subtypes. Breast Cancer Research and Treatment, 182, 581–589. https://doi.org/10.1007/s10549-020-05719-x

• Journal Article Type: Article
• Acceptance Date: Jun 1, 2020
• Online Publication Date: Jun 10, 2020
• Publication Date: Jun 10, 2020
• Deposit Date: Jun 1, 2020
• Publicly Available Date: Jun 1, 2020
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 182
• Pages: 581–589
• DOI: https://doi.org/10.1007/s10549-020-05719-x
• Keywords: BMI-1; breast cancer; oestrogen receptor positive; outcome; breast cancer stem markers
• Public URL: https://nottingham-repository.worktribe.com/output/4549639
• Publisher URL: https://link.springer.com/article/10.1007/s10549-020-05719-x
• Additional Information: Received: 27 December 2019; Accepted: 1 June 2020; First Online: 10 June 2020; : ; : The authors declare that they have no conflicts of interests.; : The experiments comply with the current laws of the country in which they were performed.; : This study was approved by the Nottingham Research Ethics Committee 2 under the title ‘Development of a molecular genetic classification of breast cancer’ and the North West—Greater Manchester Central Research Ethics Committee under the title ‘Nottingham Health Science Biobank (NHSB)’ reference number 15/NW/0685. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Release of data was also pseudoanonymised as per the UK Human Tissue Act regulations. This article does not contain any studies with animals performed by any of the authors.; : All tissue samples from Nottingham used in this study were pseudoanonymised and collected prior to 1st September 2006; therefore, under the UK Human Tissue Act, informed patient consent was not needed.