Neural Functions Play Different Roles in Triple Negative Breast Cancer (TNBC) and non-TNBC.

Triple negative breast cancer (TNBC) represents the most malignant subtype of breast cancer, and yet our understanding about its unique biology remains elusive. We have conducted a comparative computational analysis of transcriptomic data of TNBC and non-TNBC (NTNBC) tissue samples from the TCGA database, focused on genes involved in neural functions. Our main discoveries are: (1) while both subtypes involve neural functions, TNBC has substantially more up-regulated neural genes than NTNBC, suggesting that TNBC is more complex than NTNBC; (2) non-neural functions related to cell-microenvironment interactions and intracellular damage processing are key inducers of the neural genes in both TNBC and NTNBC, but the inducer-responder relationships are different in the two cancer subtypes; (3) key neural functions such as neural crest formation are predicted to enhance adaptive immunity in TNBC while glia development, along with a few other neural functions, induce both innate and adaptive immunity in NTNBC. These results reveal key differences in the biology between the two cancer subtypes, particularly in terms of the roles that neural functions play. Our findings may open new doors for further investigation of the distinct biology of TNBC vs. NTNBC.