Type

Journal Article

Authors

Darran P O'Connor
William M Gallagher
Desmond G Higgins
Karin Jirstrom
John P Crown
Finian Martin
Sara McNally
Sharon F McGee
Gabriela Gremel
Donal J Brennan
and 2 others

Subjects

Medicine & Nursing

Topics
breast cancer cancer cells disease progression cancer survival regression analysis correspondence analysis functional analysis gene expression data

miR-187 is an independent prognostic factor in breast cancer and confers increased invasive potential in vitro. (2012)

Abstract Here, we describe an integrated bioinformatics, functional analysis, and translational pathology approach to identify novel miRNAs involved in breast cancer progression. Coinertia analysis (CIA) was used to combine a database of predicted miRNA target sites and gene expression data. Using two independent breast cancer cohorts, CIA was combined with correspondence analysis and between group analysis to produce a ranked list of miRNAs associated with disease progression. Ectopic expression studies were carried out in MCF7 cells and miRNA expression evaluated in two additional cohorts of patients with breast cancer by in situ hybridization on tissue microarrays. CIA identified miR-187 as a key miRNA associated with poor outcome in breast cancer. Ectopic expression of miR-187 in breast cancer cells resulted in a more aggressive phenotype. In a test cohort (n = 117), high expression of miR-187 was associated with a trend toward reduced breast cancer-specific survival (BCSS; P = 0.058), and a significant association with reduced BCSS in lymph node-positive patients (P = 0.036). In a validation cohort (n = 470), high miR-187 was significantly associated with reduced BCSS in the entire cohort (P = 0.021) and in lymph node-positive patients (P = 0.012). Multivariate Cox regression analysis revealed that miR-187 is an independent prognostic factor in both cohorts [cohort 1: HR, 7.37; 95% confidence interval (CI), 2.05-26.51; P = 0.002; cohort 2: HR, 2.80; 95% CI, 1.52-5.16; P = 0.001] and in lymph node-positive patients in both cohorts (cohort 1: HR, 13.74; 95% CI, 2.62-72.03; P = 0.002; cohort 2: HR, 2.77; 95% CI, 1.32-5.81; P = 0.007). miR-187 expression in breast cancer leads to a more aggressive, invasive phenotype and acts as an independent predictor of outcome.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Darran P O'Connor, William M Gallagher, Desmond G Higgins, Karin Jirstrom, John P Crown, Finian Martin, Sara McNally, Sharon F McGee, Gabriela Gremel, Donal J Brennan and 2 others

Experts in our system

1
Darran P O'Connor
Royal College of Surgeons in Ireland
Total Publications: 43
 
2
William M Gallagher
University College Dublin
Total Publications: 148
 
3
Desmond G Higgins
University College Dublin
Total Publications: 76
 
4
Karin Jirstrom
University College Dublin
 
5
John Crown
Dublin City University
Total Publications: 104
 
6
Finian Martin
University College Dublin
Total Publications: 81
 
7
Sara McNally
University College Dublin
Total Publications: 12
 
8
Donal J Brennan
University College Dublin