Background: Control of DNA damage is frequently deregulated in solid tumors. Upregulation of genes within this process can be indicative of a more aggressive phenotype and linked with worse outcome. In the present article we identify DNA damage related genes associated with worse outcome in breast cancer.
Results: 2286 genes were differentially expressed between normal breast tissue and basal-like tumors, and 62 included in the DNA metabolic process function. Expression of RAD51, GINS1, TRIP13 and MCM2 were associated with detrimental relapse free survival (RFS) and overall survival (OS) in luminal tumors. The combined analyses of TRIP13+RAD51+MCM2 showed the worse association for RFS (HR 2.25 (1.51-3.35) log rank p= 4.1e-05) and TRIP13+RAD51 for OS (HR 5.13 (0.6-44.17) log rank p=0.098) in ER+/HER2- tumors. TRIP13 is amplified in 3.1% of breast cancers.
Methods: Transcriptomic analyses using public datasets evaluating expression values between normal breast tissue and TNBC identified upregulated genes. Genes included in the DNA metabolic process were selected and confirmed using data contained at oncomine (www.oncomine.org). Evaluation of the selected genes with RFS and OS was performed using the KM Plotter Online Tool (http://www.kmplot.com). Evaluation of molecular alterations was performed using cBioportal (www.cbioportal.org).
Conclusions: Expression of DNA metabolic related genes RAD51, GINS1, TRIP13 and MCM2 are associated with poor outcome. Combinations of some of these genes are linked to poor RFS or OS in luminal A, B and ER+HER2- tumors. Evaluation of its predictive capacity in prospective studies is required.
Keywords: GINS1; MCM2; RAD51; TRIP13; breast cancer outcome.