Elevated expression of Aurora-A/AURKA in breast cancer associates with younger age and aggressive features.

BACKGROUND AND 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: 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: 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: 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.

Prevalence of depressive disorder among patients with fibromyalgia: Systematic review and meta-analysis.

BACKGROUND: It is acknowledged that fibromyalgia (FM) as a medical (rheumatological) disorder and major depressive disorder (MDD) as a mental disorder often co-occurs, but the inconsistency is prevailing at study-level and no overall estimate of the co-occurrence exist. AIMS: This systematic review and meta-analysis aimed to estimate the overall point- and life-time prevalence of MDD among FM patients based on structured clinical interviews (SCI); and to estimate the point-prevalence of MDD among FM patients based on screening symptom scales (SSS). METHOD: The electronical databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO were searched for papers that reported on prevalence of MDD among FM patients. Eligible studies were included in a random effects meta-analysis pooling the prevalence of depression. RESULTS: The literature search identified 11 eligible studies for the meta-analysis. For SCI, the overall pooled point-prevalence (PP) was 25% (95% CI 19 to 31%), and life-time prevalence (LP) was 65% (95% CI 59 to 71%). When estimating the PP with self-administered SSS the overall pooled PP was 45% (95% CI 32 to 59%), and a single clinician-administered SSS yielded a PP of 23% (95% CI 10 to 41%). There was low inconsistency for the SCI and high inconsistency for the SSS. CONCLUSION: One fourth of all FM patients had MDD, and more than half experienced MDD during their life-time according to clinician-administered instruments. Prevalence of MDD was almost twice as high when using self-administered symptom scales and may be likely to overestimate the co-occurrence.