Transcriptomic analyses identify key differentially expressed genes and clinical outcomes between triple-negative and non-triple-negative breast cancer

Bo Chen,1,* Hailin Tang,2,* Xi Chen,3,* Guochun Zhang,1 Yulei Wang,1 Xiaoming Xie,2 Ning Liao1 1Department of Breast Cancer, Cancer Center, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China; 2Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; 3Department of Anatomy, Hengyang Medical College, University of South China, Hengyang, China *These authors contributed equally to this work 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, transcriptom