Triple Negative Breast Cancer: A Multi-Omics Network Discovery Strategy for Candidate Targets and Driving Pathways

Abstract

Triple negative breast cancer (TNBC) represents approximately 15% of breast cancers and is characterized by lack of expression of both estrogen receptor (ER) and progesterone receptor (PR), together with absence of human epidermal growth factor 2 (HER2). TNBC has attracted considerable attention due to its aggressiveness such as large tumor size, high proliferation rate, and metastasis. The absence of clinically efficient molecular targets is of great concern in treatment of patients with TNBC. In light of the complexity of TNBC, we applied a systematic and integrative transcriptomics and interactomics approach utilizing transcriptional regulatory and protein-protein interaction networks to discover putative transcriptional control mechanisms of TNBC. To this end, we identified TNBC-driven molecular pathways such as the Janus kinase-signal transducers, and activators of transcription (JAK-STAT) and tumor necrosis factor (TNF) signaling pathways. The multi-omics molecular target and biomarker discovery approach presented here can offer ways forward on novel diagnostics and potentially help to design personalized therapeutics for TNBC in the future.