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

Abstract

Purpose BMI1, 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 method BMI1 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. Result BMI1 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. Conclusion High 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.

Schisandrin B inhibits epithelial‑mesenchymal transition and stemness of large‑cell lung cancer cells and tumorigenesis in xenografts via inhibiting the NF‑κB and p38 MAPK signaling pathways

“…Oct-4 is also a CSC marker whose expression enhances features of CSCs ( 32 ). In addition, Bmi-1 behaves as a key regulator in the self-renewal, differentiation and tumor initiation and is thus widely used as a CSC marker ( 33 ). In addition to the proportion of CD133 + cells in induced cells and sphere formation of induced cells, the expression levels of CSC markers (CD44, Oct-4 and Bmi-1), as well as cell cycle, were detected in induced cells and protocells to confirm that cells used in the present study were CSCs and not a CSC-enriched population.…”

Sustained inactivation of the Polycomb PRC1 complex induces DNA repair defects and genomic instability in epigenetic tumors

“…PRC1 and PRC2 co-regulate a variety of cellular processes including embryonic development, differentiation, and cell proliferation ( Chan and Morey 2019 , Loubiere, Martinez and Cavalli 2019 , Loubiere, Papadopoulos et al 2020 ). Consistent with a role for PcG proteins in cell identity, dysregulation of these components has been associated with multiple types of cancer ( Piunti and Shilatifard 2021 ), including breast and prostate cancers, as well as hematologic malignancies ( Varambally, Dhanasekaran et al 2002 , Guo, Zeng et al 2007 , Li, Li et al 2010 , Zhang, Sheng et al 2010 , Ntziachristos, Tsirigos et al 2012 , Herviou, Cavalli et al 2016 , Kim and Roberts 2016 , Althobiti, Muftah et al 2020 ). In agreement, PRC1 loss-of-function mutations in Drosophila result in up-regulation of major oncogenes including JAK/STAT, NOTCH and JNK signaling pathways, which are important drivers of the tumorigenic process ( Classen, Bunker et al 2009 , Martinez, Schuettengruber et al 2009 , Loubiere, Delest et al 2016 , Torres, Monti et al 2018 ).…”

High BMI1 Expression with Low CD8+ and CD4+ T Cell Activity Could Promote Breast Cancer Cell Survival: A Machine Learning Approach

“…A study by Althobiti et al demonstrated that high BMI1 expression was associated with better prognosis in patients with luminal ER-positive breast cancer, but was associated with a poorer survival rate in patients with the triple-negative subtype. In patients with the HER2-positive subtype, there was no significant difference in survival [ 39 ]. Another study reported that high BMI1 expression could promote tamoxifen resistance in ER-positive breast cancers, with a high recurrence rate [ 23 ].…”