Deciphering clinical significance of BCL11A isoforms and protein expression roles in triple-negative breast cancer subtype.
BCL11A expression
BCL11A isoforms
BCL11A mutations
Survival analysis
Triple negative breast cancer
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
11
07
2022
accepted:
15
08
2022
medline:
5
7
2023
pubmed:
29
8
2022
entrez:
28
8
2022
Statut:
ppublish
Résumé
Triple negative breast cancer (TNBC) is an aggressive clinical tumor, accounting for about 25% of breast cancer (BC) related deaths. Chemotherapy is the only therapeutic option to treat TNBC, hence a detailed understanding of the biology and its categorization is required. To investigate the clinical relevance of BCL11A in TNBC subtype, we focused on gene and protein expression and its mutational status in a large cohort of this molecular subtype. Gene expression profiling of BCL11A and its isoforms (BCL11A-XL, BCL11A-L and BCL11A-S) has been determined in Luminal A, Luminal B, HER2-enriched and TNBC subtypes. BCL11A protein expression has been analyzed by immunohistochemistry (IHC) and its mutational status by Sanger sequencing. In our study, BCL11A was significantly overexpressed in TNBC both at transcriptional and translational levels compared to other BC molecular subtypes. A total of 404 TNBCs were selected and examined showing a high prevalence of BCL11A-XL (37.3%) and BCL11A-L (31.4%) isoform expression in TNBC, associated with a 26% of BCL11A protein expression levels. BCL11A protein expression predicts scarce LIV (HR = 0.52; 95% CI, 0.29-0.92, P = 0.03) and AR downregulation (HR = 0.37; 95% CI, 0.16-0.88; P = 0.02), as well as a higher proliferative index in TNBC cells. BCL11A-L expression is associated with more aggressive TNBC histological types, such as medullary and metaplastic carcinoma. Our finding showed that BCL11A protein expression acts as an unfavorable prognostic factor in TNBC patients, especially in non luminal TNBCs subgroups. These results may yield a better treatment strategy by providing a new parameter for TNBC classification.
Identifiants
pubmed: 36030436
doi: 10.1007/s00432-022-04301-w
pii: 10.1007/s00432-022-04301-w
pmc: PMC10314865
doi:
Substances chimiques
Transcription Factors
0
BCL11A protein, human
0
Repressor Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3951-3963Subventions
Organisme : Fondazione di Sardegna 2021, Italy
ID : 0494
Organisme : Fondo di Ateneo per la Ricerca 2020-University of Sassari
ID : 2020
Informations de copyright
© 2022. The Author(s).
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