Transcriptomic Analysis of Subtype-Specific Tyrosine Kinases as Triple Negative Breast Cancer Biomarkers

SIMPLE SUMMARY: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with a higher mortality rate when compared to the other subtypes. Because of the absence of a molecular target and the heterogeneity of TNBC molecular subtypes, the development of targeted therapies is limited. Protein tyrosine kinases (TKs), in particular, have emerged as important molecular targets and biomarkers in cancer. Thus, we identified the signature TK of individual TNBC subtypes by analyzing RNA-seq-based transcriptome data of TNBC patients from The Cancer Genome Atlas database and validated this finding against other TNBC patients and cell line datasets. Our discovery of the signature TK for TNBC subtypes can be used as actionable targets for anti-cancer therapies, as well as subtype-specific biomarkers for TNBC. ABSTRACT: Triple negative breast cancer (TNBC) shows impediment to the development of targeted therapies due to the absence of specific molecular targets. The high heterogeneity across TNBC subtypes, which can be classified to be at least four subtypes, including two basal-like (BL1, BL2), a mesenchymal (M), and a luminal androgen receptor (LAR) subtype, limits the response to cancer therapies. Despite many attempts to identify TNBC biomarkers, there are currently no effective targeted therapies against this malignancy. In this study, thus, we identified the potential tyrosine kinase (TK) genes that are uniquely expressed in each TNBC subtype, since TKs have been typically used as drug targets. Differentially expressed TK genes were analyzed from The Cancer Genome Atlas (TCGA) database and were confirmed with the other datasets of both TNBC patients and cell lines. The results revealed that each TNBC subtype expressed distinct TK genes that were specific to the TNBC subtype. The identified subtype-specific TK genes of BL1, BL2, M, and LAR are LYN, CSF1R, FGRF2, and SRMS, respectively. These findings could serve as a potential biomarker of specific TNBC subtypes, which could lead to an effective treatment for TNBC patients.