Decreased expression of key tumour suppressor microRNAs is associated with lymph node metastases in triple negative breast cancer.
BACKGROUND
Breast cancer is the most common malignancy that develops in women, responsible for the highest cancer-associated death rates. Triple negative breast cancers represent an important subtype that have an aggressive clinical phenotype, are associated with a higher likelihood of metastasis and are not responsive to current targeted therapies. miRNAs have emerged as an attractive candidate for molecular biomarkers and treatment targets in breast cancer, but their role in the progression of triple negative breast cancer remains largely unexplored.


METHODS
This study has investigated miRNA expression profiles in 31 primary triple negative breast cancer cases and in 13 matched lymph node metastases compared with 23 matched normal breast tissues to determine miRNAs associated with the initiation of this disease subtype and those associated with its metastasis.


RESULTS
71 miRNAs were differentially expressed in triple negative breast cancer, the majority of which have previously been associated with breast cancer, including members of the miR-200 family and the miR-17-92 oncogenic cluster, suggesting that the majority of miRNAs involved in the initiation of triple negative breast cancer are not subtype specific. However, the repertoire of miRNAs expressed in lymph node negative and lymph node positive triple negative breast cancers were largely distinct from one another. In particular, miRNA profiles associated with lymph node negative disease tended to be up-regulated, while those associated with lymph node positive disease were down-regulated and largely overlapped with the profiles of their matched lymph node metastases. From this, 27 miRNAs were identified that are associated with metastatic capability in the triple negative breast cancer subtype.


CONCLUSIONS
These results provide novel insight into the repertoire of miRNAs that contribute to the initiation of and progression to lymph node metastasis in triple negative breast cancer and have important implications for the treatment of this breast cancer subtype.
Centre for Information-Based Medicine, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia. Kelly.Kiejda@newcastle.edu.au.
Kelly A
KA
Avery-Kiejda
Stephen G
SG
Braye
Andrea
A
Mathe
John F
JF
Forbes
Rodney J
RJ
Scott
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000235:genetics* / Q000556:secondary; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D064726:Triple Negative Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; D035683:MicroRNAs