Mathe Andrea, Wong-Brown Michelle, Morten Brianna, Forbes John F, Braye Stephen G, Avery-Kiejda Kelly A, Scott Rodney J
Centre for Information Based Medicine, Hunter Medical Research Institute, NSW, 2305, Australia.
Priority Research Centre for Cancer, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, NSW, 2308, Australia.
Sci Rep. 2015 Nov 5;5:15832. doi: 10.1038/srep15832.
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.
三阴性乳腺癌(TNBC)是最具侵袭性的乳腺癌亚型,预后最差且没有靶向治疗方法。与其他乳腺癌亚型患者相比,TNBC患者更易发生转移和复发。我们旨在鉴定TNBC特异性基因以及与淋巴结转移相关的基因,淋巴结转移是转移扩散的首要迹象之一。总共使用了33例TNBC样本;其中17例有匹配的相邻正常组织,15例有匹配的淋巴结转移样本。采用基因表达微阵列分析来揭示这些组之间差异表达的基因。我们鉴定并验证了66个在肿瘤与相邻正常样本比较时显著改变的基因。此外,我们鉴定了83个与淋巴结转移相关的基因,并将这些基因与miRNA表达相关联。通路分析揭示了它们参与DNA修复、重组和细胞死亡、染色体不稳定以及其他已知的癌症相关通路。最后,鉴定出了4个TNBC特异性基因,其中一个与总生存期相关。本研究鉴定出了参与TNBC淋巴结转移的新基因以及TNBC特异性基因,这些基因未来可能用作治疗靶点或预后指标。