Purpose: There are significant differences in the biological behavior between triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (non-TNBC). In the present study, we identify key differential genes and clinical outcomes between TNBC and non-TNBC.
Materials and methods: Transcriptomic analyses used GEO datasets (GSE76275), gene ontology, KEGG pathway analysis and cBioPortal. Quantitative RT-PCR analysis (qRT-PCR) was used to validate the differentially expressed genes. We used the KM Plotter Online Tool and 240 patients with TNBC tissue microarray to assay the prognostic value of HORMAD1 .
Results: The upregulated differentially expressed genes were enriched in transcription factor activity, sequence-specific DNA binding and nucleic acid binding transcription factor activity. Only 16 genes were upregulated when further screened for fold change >4-fold change. HORMAD1  and SOX8  exhibited high frequencies of change of greater than 10% (HORMAD1  was close to 20%). qRT-PCR results indicated that HORMAD1  and SOX8  mRNA levels were significantly upregulated in TNBC samples. In KM Plotter Online Tool, high HORMAD1  was associated with worse outcome. In our tissue microarray (including 240 TNBC tissues), IHC analysis revealed that 29.7% (55/240) of the tumor samples exhibited high HORMAD1  expression and 70.3% (185/240) of the tumor samples exhibited low HORMAD1  expression levels. Meanwhile, high HORMAD1  group has a bad prognosis.
Conclusion: The status of transcriptional activation is an important difference between TNBC and non-TNBC. HORMAD1  is a key differential gene associated with poor outcome in TNBC. Epigenetic therapy and agents targeting cancer/testis antigens might potentially help to customize therapies of TNBC.
Keywords: HORMAD1 , triple-negative breast cancer, non-triple-negative breast cancer, prognostic factor, transcriptome