Document Detail


Validation of expression patterns for nine miRNAs in 204 lymph-node negative breast cancers.
MedLine Citation:
PMID:  23144930     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: Although lymph node negative (LN-) breast cancer patients have a good 10-years survival (∼85%), most of them still receive adjuvant therapy, while only some benefit from this. More accurate prognostication of LN- breast cancer patient may reduce over- and under-treatment. Until now proliferation is the strongest prognostic factor for LN- breast cancer patients. The small molecule microRNA (miRNA) has opened a new window for prognostic markers, therapeutic targets and/or therapeutic components. Previously it has been shown that miR-18a/b, miR-25, miR-29c and miR-106b correlate to high proliferation.
METHODS: The current study validates nine miRNAs (miR-18a/b miR-25, miR-29c, miR-106b, miR375, miR-424, miR-505 and let-7b) significantly correlated with established prognostic breast cancer biomarkers. Total RNA was isolated from 204 formaldehyde-fixed paraffin embedded (FFPE) LN- breast cancers and analyzed with quantitative real-time Polymerase Chain Reaction (qPCR). Independent T-test was used to detect significant correlation between miRNA expression level and the different clinicopathological features for breast cancer.
RESULTS: Strong and significant associations were observed for high expression of miR-18a/b, miR-106b, miR-25 and miR-505 to high proliferation, oestrogen receptor negativity and cytokeratin 5/6 positivity. High expression of let-7b, miR-29c and miR-375 was detected in more differentiated tumours. Kaplan-Meier survival analysis showed that patients with high miR-106b expression had an 81% survival rate vs. 95% (P = 0.004) for patients with low expression.
CONCLUSION: High expression of miR-18a/b are strongly associated with basal-like breast cancer features, while miR-106b can identify a group with higher risk for developing distant metastases in the subgroup of Her2 negatives. Furthermore miR-106b can identify a group of patients with 100% survival within the otherwise considered high risk group of patients with high proliferation. Using miR-106b as a biomarker in conjunction to mitotic activity index could thereby possibly save 18% of the patients with high proliferation from overtreatment.
Authors:
Kristin Jonsdottir; Susanne R Janssen; Fabiana C Da Rosa; Einar Gudlaugsson; Ivar Skaland; Jan P A Baak; Emiel A M Janssen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Validation Studies     Date:  2012-11-07
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-11-12     Completed Date:  2013-05-09     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e48692     Citation Subset:  IM    
Affiliation:
Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Breast Neoplasms / diagnosis,  genetics*,  pathology
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Humans
Kaplan-Meier Estimate
Lymph Nodes / pathology
MicroRNAs / analysis,  genetics,  metabolism
Middle Aged
Prognosis
Receptors, Estrogen / metabolism
Survival Rate
Tumor Markers, Biological / analysis,  genetics
Chemical
Reg. No./Substance:
0/MIRN106 microRNA, human; 0/MIRN25 microRNA, human; 0/MIRN29 microRNA, human; 0/MIRN424 microrna, human; 0/MIRN505 microRNA, human; 0/MIrn181 microRNA, human; 0/MicroRNAs; 0/Receptors, Estrogen; 0/Tumor Markers, Biological; 0/mirnlet7 microRNA, human
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