Elevated expression of Aurora-A/AURKA in breast cancer associates with younger age and aggressive features.
Journal
Breast cancer research : BCR
ISSN: 1465-542X
Titre abrégé: Breast Cancer Res
Pays: England
ID NLM: 100927353
Informations de publication
Date de publication:
28 Aug 2024
28 Aug 2024
Historique:
received:
30
01
2024
accepted:
16
08
2024
medline:
31
8
2024
pubmed:
31
8
2024
entrez:
28
8
2024
Statut:
epublish
Résumé
Aurora kinase A (AURKA) is reported to be overexpressed in breast cancer. In addition to its role in regulating cell cycle and mitosis, studies have reported AURKA involvements in oncogenic signaling in suppressing BRCA1 and BRCA2. We aimed to characterize AURKA protein and mRNA expression in a breast cancer cohort of the young, investigating its relation to clinico-pathologic features and survival, and exploring age-related AURKA-associated biological processes. Aurora kinase A immunohistochemical staining was performed on tissue microarrays of primary tumors from an in-house breast cancer cohort (n = 355) with information on clinico-pathologic data, molecular markers, and long and complete follow-up. A subset of the in-house cohort (n = 127) was studied by the NanoString Breast Cancer 360 expression panel for exploration of mRNA expression. METABRIC cohorts < 50 years at breast cancer diagnosis (n = 368) were investigated for differentially expressed genes and enriched gene sets in AURKA mRNA high tumors stratified by age. Differentially expressed genes and gene sets were investigated using network analyses and g:Profiler. High Aurora kinase A protein expression associated with aggressive clinico-pathologic features, a basal-like subtype, and high risk of recurrence score. These patterns were confirmed using mRNA data. High AURKA gene expression demonstrated independent prognostic value when adjusted for traditional clinico-pathologic features and molecular subtypes. Notably, high AURKA expression significantly associated with reduced disease-specific survival within patients below 50 years, also within the luminal A subtype. Tumors of high AURKA expression showed gene expression patterns reflecting increased DNA damage activation and higher BRCAness score. Our findings indicate higher AURKA expression in young breast cancer, and associations between high Aurora-A/AURKA and aggressive tumor features, including higher tumor cell proliferation, and shorter survival, in the young. Our findings point to AURKA as a marker for increased DNA damage and DNA repair deficiency and suggest AURKA as a biomarker of clinical relevance in young breast cancer.
Sections du résumé
BACKGROUND AND OBJECTIVE
OBJECTIVE
Aurora kinase A (AURKA) is reported to be overexpressed in breast cancer. In addition to its role in regulating cell cycle and mitosis, studies have reported AURKA involvements in oncogenic signaling in suppressing BRCA1 and BRCA2. We aimed to characterize AURKA protein and mRNA expression in a breast cancer cohort of the young, investigating its relation to clinico-pathologic features and survival, and exploring age-related AURKA-associated biological processes.
METHODS
METHODS
Aurora kinase A immunohistochemical staining was performed on tissue microarrays of primary tumors from an in-house breast cancer cohort (n = 355) with information on clinico-pathologic data, molecular markers, and long and complete follow-up. A subset of the in-house cohort (n = 127) was studied by the NanoString Breast Cancer 360 expression panel for exploration of mRNA expression. METABRIC cohorts < 50 years at breast cancer diagnosis (n = 368) were investigated for differentially expressed genes and enriched gene sets in AURKA mRNA high tumors stratified by age. Differentially expressed genes and gene sets were investigated using network analyses and g:Profiler.
RESULTS
RESULTS
High Aurora kinase A protein expression associated with aggressive clinico-pathologic features, a basal-like subtype, and high risk of recurrence score. These patterns were confirmed using mRNA data. High AURKA gene expression demonstrated independent prognostic value when adjusted for traditional clinico-pathologic features and molecular subtypes. Notably, high AURKA expression significantly associated with reduced disease-specific survival within patients below 50 years, also within the luminal A subtype. Tumors of high AURKA expression showed gene expression patterns reflecting increased DNA damage activation and higher BRCAness score.
CONCLUSIONS
CONCLUSIONS
Our findings indicate higher AURKA expression in young breast cancer, and associations between high Aurora-A/AURKA and aggressive tumor features, including higher tumor cell proliferation, and shorter survival, in the young. Our findings point to AURKA as a marker for increased DNA damage and DNA repair deficiency and suggest AURKA as a biomarker of clinical relevance in young breast cancer.
Identifiants
pubmed: 39198859
doi: 10.1186/s13058-024-01882-x
pii: 10.1186/s13058-024-01882-x
doi:
Substances chimiques
Aurora Kinase A
EC 2.7.11.1
Biomarkers, Tumor
0
AURKA protein, human
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
126Subventions
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : Helse Vest Research Fund
ID : F-12143
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Organisme : University of Bergen, Research Council of Norway, Center of Excellence funding scheme
ID : 223250
Informations de copyright
© 2024. The Author(s).
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