Advanced

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

O'Brien, Sallyarm L.; Fagan, Ailis; Fox, Edward J. P.; Millikan, Robert C.; Culhane, Aedin C.; Brennan, Donal J.; McCann, Amanda H.; Hegarty, Shauna; Moyna, Siobhan and Duffy, Michael J., et al. (2007) In International Journal of Cancer 120(7). p.1434-1443
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... (More)
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. (c) 2007 Wiley-Liss, Inc. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CENP-F, prognosis, tissue microarrays, breast cancer, DNA microarrays, chromosomal instability
in
International Journal of Cancer
volume
120
issue
7
pages
1434 - 1443
publisher
John Wiley & Sons
external identifiers
  • wos:000244610700008
  • scopus:33847688152
ISSN
0020-7136
DOI
10.1002/ijc.22413
language
English
LU publication?
yes
id
69bbd541-78c3-4620-b74c-24062cc40353 (old id 672666)
date added to LUP
2007-12-14 12:44:42
date last changed
2017-08-27 04:15:25
@article{69bbd541-78c3-4620-b74c-24062cc40353,
  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 &lt; 0.001) and reduced metastasis-free survival (p &lt; 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. (c) 2007 Wiley-Liss, Inc.},
  author       = {O'Brien, Sallyarm L. and Fagan, Ailis and Fox, Edward J. P. and Millikan, Robert C. and Culhane, Aedin C. and Brennan, Donal J. and McCann, Amanda H. and Hegarty, Shauna and Moyna, Siobhan and Duffy, Michael J. and HigginS, Desmond G. and Jirström, Karin and Landberg, Göran and Gallagher, William M.},
  issn         = {0020-7136},
  keyword      = {CENP-F,prognosis,tissue microarrays,breast cancer,DNA microarrays,chromosomal instability},
  language     = {eng},
  number       = {7},
  pages        = {1434--1443},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer},
  url          = {http://dx.doi.org/10.1002/ijc.22413},
  volume       = {120},
  year         = {2007},
}