Novel genes associated with lymph node metastasis in triple negative breast cancer

• DOI: 10.1038/srep15832
• Publication Date: 2015-11-05T09:05:24Z
• Authors: Andrea Mathe; Michelle Wong-Brown; Brianna Morten; John F. Forbes; Stephen G. Braye; Kelly A. Avery-Ki...; Rodney J. Scott
• Keywords: Adult; 0301 basic medicine; DNA Repair; Triple Negative Breast Neoplasms; Article; 03 medical and health sciences; breast cancer; triple negative breast cancer (TNBC); breast cancer genes; Chromosomal Instability; 616; Biomarkers, Tumor; Humans; Breast; Aged; Recombination, Genetic; Cell Death; Middle Aged; Prognosis; breast cancer subtypes; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; Lymphatic Metastasis; Female; Lymph Nodes

AbstractTriple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and no targeted treatments. TNBC patients are more likely to develop metastases and relapse than patients with other breast cancer subtypes. We aimed to identify TNBC-specific genes and genes associated with lymph node metastasis, one of the first signs of metastatic spread. A total of 33 TNBCs were used; 17 of which had matched normal adjacent tissues available and 15 with matched lymph node metastases. Gene expression microarray analysis was used to reveal genes that were differentially expressed between these groups. We identified and validated 66 genes that are significantly altered when comparing tumours to normal adjacent samples. Further, we identified 83 genes that are associated with lymph node metastasis and correlated these with miRNA-expression. Pathway analysis revealed their involvement in DNA repair, recombination and cell death, chromosomal instability and other known cancer-related pathways. Finally, four genes were identified that were specific for TNBC, of which one was associated with overall survival. This study has identified novel genes involved in LN metastases in TNBC and genes that are TNBC specific that may be used as treatment targets or prognostic indicators in the future.