Stathmin expression associates with vascular and immune responses in aggressive breast cancer subgroups.
BRCA1 Protein
/ genetics
Breast
/ metabolism
Breast Neoplasms
/ blood supply
Cell Line, Tumor
Cell Proliferation
/ drug effects
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Germ-Line Mutation
/ genetics
Humans
Kaplan-Meier Estimate
Logistic Models
Neoplasm Invasiveness
Phenotype
Phosphatidylinositol 3-Kinases
/ metabolism
Phosphoinositide-3 Kinase Inhibitors
/ pharmacology
RNA, Messenger
/ genetics
Receptors, Estrogen
/ metabolism
Stathmin
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 02 2020
19 02 2020
Historique:
received:
18
10
2019
accepted:
31
01
2020
entrez:
21
2
2020
pubmed:
23
2
2020
medline:
13
11
2020
Statut:
epublish
Résumé
Studies indicate that stathmin expression associates with PI3K activation in breast cancer, suggesting stathmin as a marker for targetable patient subgroups. Here we assessed stathmin in relation to tumour proliferation, vascular and immune responses, BRCA1 germline status, basal-like differentiation, clinico-pathologic features, and survival. Immunohistochemical staining was performed on breast cancers from two series (cohort 1, n = 187; cohort 2, n = 198), and mass spectrometry data from 24 cases and 12 breast cancer cell lines was examined for proteomic profiles. Open databases were also explored (TCGA, METABRIC, Oslo2 Landscape cohort, Cancer Cell Line Encyclopedia). High stathmin expression associated with tumour proliferation, p53 status, basal-like differentiation, BRCA1 genotype, and high-grade histology. These patterns were confirmed using mRNA data. Stathmin mRNA further associated with tumour angiogenesis, immune responses and reduced survival. By logistic regression, stathmin protein independently predicted a BRCA1 genotype (OR 10.0, p = 0.015) among ER negative tumours. Cell line analysis (Connectivity Map) implied PI3K inhibition in tumours with high stathmin. Altogether, our findings indicate that stathmin might be involved in the regulation of tumour angiogenesis and immune responses in breast cancer, in addition to tumour proliferation. Cell data point to potential effects of PI3K inhibition in tumours with high stathmin expression.
Identifiants
pubmed: 32076022
doi: 10.1038/s41598-020-59728-3
pii: 10.1038/s41598-020-59728-3
pmc: PMC7031232
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
Phosphoinositide-3 Kinase Inhibitors
0
RNA, Messenger
0
Receptors, Estrogen
0
STMN1 protein, human
0
Stathmin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2914Références
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