Abstract
Triple 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.
Highlights
Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and no targeted treatments
In this study we have identified a gene expression profile in a series of TNBC patients where we were able to examine tumour tissue, normal adjacent tissue and lymph node metastases from the same patient and compared that to tumours derived from patients who did not have any metastatic disease
We compared the gene expression of 33 grade 3 primary invasive ductal carcinomas (IDCs) to 17 normal adjacent tissue (NAT) samples (Supplementary Table 1) to reveal gene and lncRNA transcripts significantly associated with TNBC
Summary
Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and no targeted treatments. 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. There are several trials with newer disease specific agents that include, poly (ADP-ribose) polymerase (PARP) inhibitors, angiogenesis inhibitors, EGFR-targeted agents, src kinase inhibitors, an androgen receptor inhibitor (bicalutamide), epigenetic targeting, and PI3K-pathway inhibition[1,8] None of these trials have far been associated with any significant improvement in TNBC patients. MiRNAs regulate multiple biological processes including proliferation, cell death, development, genomic stability, and EMT10,11—key processes in tumour development identified by Weinberg and Hanahan They regulate normal physiological change but are involved in pathological conditions, such as cancer[12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
