Type

Journal Article

Authors

William M Gallagher
Goran Landberg
Karin Jirstrom
Desmond G Higgins
Michael J Duffy
Siobhan Moyna
Shauna Hegarty
Amanda H McCann
Donal J Brennan
Aedín C Culhane
and 4 others

Subjects

Biochemistry

Topics
humans tissue array analysis gene amplification female genetics metabolism oligonucleotide array sequence analysis centromere middle aged pathology receptors estrogen phosphorylation physiology survival rate lymphatic metastasis prognosis immunoenzyme techniques centromere protein f tumor markers biological rna neoplasm gene expression regulation neoplastic chromosomal proteins non histone gene expression profiling ki 67 antigen breast neoplasms microfilament proteins follow up studies vascular endothelial growth factor receptor 2 chromosomal instability proto oncogene protein c ets 2 adult

CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer. (2007)

Abstract DNA microarrays have the potential to classify tumors according to their transcriptome. Tissue microarrays (TMAs) facilitate the validation of biomarkers by offering a high-throughput approach to sample analysis. We reanalyzed a high profile breast cancer DNA microarray dataset containing 96 tumor samples using a powerful statistical approach, between group analyses. Among the genes we identified was centromere protein-F (CENP-F), a gene associated with poor prognosis. In a published follow-up breast cancer DNA microarray study, comprising 295 tumour samples, we found that CENP-F upregulation was significantly associated with worse overall survival (p<0.001) and reduced metastasis-free survival (p<0.001). To validate and expand upon these findings, we used 2 independent breast cancer patient cohorts represented on TMAs. CENP-F protein expression was evaluated by immunohistochemistry in 91 primary breast cancer samples from cohort I and 289 samples from cohort II. CENP-F correlated with markers of aggressive tumor behavior including ER negativity and high tumor grade. In cohort I, CENP-F was significantly associated with markers of CIN including cyclin E, increased telomerase activity, c-Myc amplification and aneuploidy. In cohort II, CENP-F correlated with VEGFR2, phosphorylated Ets-2 and Ki67, and in multivariate analysis, was an independent predictor of worse breast cancer-specific survival (p=0.036) and overall survival (p=0.040). In conclusion, we identified CENP-F as a biomarker associated with poor outcome in breast cancer and showed several novel associations of biological significance.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

William M Gallagher, Goran Landberg, Karin Jirstrom, Desmond G Higgins, Michael J Duffy, Siobhan Moyna, Shauna Hegarty, Amanda H McCann, Donal J Brennan, Aedín C Culhane and 4 others

Experts in our system

1
William M Gallagher
University College Dublin
Total Publications: 148
 
2
Karin Jirstrom
University College Dublin
 
3
Desmond G Higgins
University College Dublin
Total Publications: 76
 
4
Michael J Duffy
University College Dublin
 
5
Amanda McCann
University College Dublin
Total Publications: 41
 
6
Donal J Brennan
University College Dublin