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Stathmin expression associates with vascular and immune responses in aggressive breast cancer subgroups.

ABSTRACT: 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.

SUBMITTER: Askeland C

PROVIDER: S-EPMC7031232 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Stathmin expression associates with vascular and immune responses in aggressive breast cancer subgroups.

Askeland Cecilie C Wik Elisabeth E Finne Kenneth K Birkeland Even E Arnes Jarle B JB Collett Karin K Knutsvik Gøril G Krüger Kristi K Davidsen Benedicte B Aas Turid T Eide Geir Egil GE Stefansson Ingunn M IM Foulkes William D WD Akslen Lars A LA

Scientific reports 20200219 1

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 ca ...[more]

PMID: 32076022

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Project description:Background and objectiveAurora 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.MethodsAurora 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.ResultsHigh 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.ConclusionsOur 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.

Dataset Information

Stathmin expression associates with vascular and immune responses in aggressive breast cancer subgroups.

Publications

Stathmin expression associates with vascular and immune responses in aggressive breast cancer subgroups.

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