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

Mulrane, Laoighse, Madden, Stephen F., Brennan, Donal J., Gremel, Gabriela, McGee, Sharon F., McNally, Sara, Martin, Finian, Crown, John P., Jirstroem, Karin, Higgins, Desmond G., Gallagher, William M. and O'Connor, Darran P. (2012) miR-187 is an independent prognostic factor in breast cancer and confers increased invasive potential in vitro. Clinical Cancer Research, 18 24: 6702-6713. doi:10.1158/1078-0432.CCR-12-1420

Author Mulrane, Laoighse
Madden, Stephen F.
Brennan, Donal J.
Gremel, Gabriela
McGee, Sharon F.
McNally, Sara
Martin, Finian
Crown, John P.
Jirstroem, Karin
Higgins, Desmond G.
Gallagher, William M.
O'Connor, Darran P.
Title miR-187 is an independent prognostic factor in breast cancer and confers increased invasive potential in vitro
Journal name Clinical Cancer Research   Check publisher's open access policy
ISSN 1078-0432
Publication date 2012-12
Sub-type Article (original research)
DOI 10.1158/1078-0432.CCR-12-1420
Volume 18
Issue 24
Start page 6702
End page 6713
Total pages 12
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Collection year 2013
Language eng
Formatted abstract
Purpose: Here, we describe an integrated bioinformatics, functional analysis, and translational pathology approach to identify novel miRNAs involved in breast cancer progression.

Experimental Design: 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.

Results: 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).

Conclusions: miR-187 expression in breast cancer leads to a more aggressive, invasive phenotype and acts as an independent predictor of outcome.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
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