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Abstract
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.
Highlights
Triple negative breast cancer (TNBC) is a most malignant subtype of breast cancer as it is more aggressive and easier to metastasize compared to the other subtypes[1,2]
Our main findings are: (i) numerous neural genes are found up-regulated in both TNBC and NTNBC, but TNBCs have considerably more such genes than in NTNBC, indicating that TNBCs have higher levels of neural functions; (ii) neural genes are transcriptionally correlated with genes involved in cell-microenvironment interactions and intracellular damage response processes in both TNBC and NTNBC but with different co-expression patterns between the subtypes; (iii) substantially more neural functions are utilized in TNBC than in NTNBC; (iv) genes involved in neural crest development and neurotransmitter secretion are predicted to regulate adaptive immunity and cell cycle only in TNBC, while genes relevant to glia development seem to promote both innate and adaptive immunity, as well as cell cycle regulation in NTNBC
To further our understanding of the functions played by neural genes in breast cancer, we have examined the functions of the up-regulated non-neural genes that are positively correlated with the expressed neural genes, referred to as NNCN. 4,233 and 598 such genes are identified in TNBC and NTNBC, respectively
Summary
Triple negative breast cancer (TNBC) is a most malignant subtype of breast cancer as it is more aggressive and easier to metastasize compared to the other subtypes[1,2]. The detailed functional roles by the neural systems in cancer formation and development, in breast cancer, remain elusive. Previous studies have been largely focused on roles played by the sympathetic and parasympathetic nerves in cancer development[16,17,18], where the two together make the autonomic nerves, a subtype of the efferent nerve, while the functional roles by other components of the nervous system are largely unknown in cancer formation. We present a computational study of transcriptomic data of TNBCs and non-TNBCs (or NTNBCs) in the TCGA database focusing on the distinct functional roles played by the neural system throughout the development of the two subtypes of breast cancers[23,24]. Our main findings are: (i) numerous neural genes are found up-regulated in both TNBC and NTNBC, but TNBCs have considerably more such genes than in NTNBC, indicating that TNBCs have higher levels of neural functions; (ii) neural genes are transcriptionally correlated with genes involved in cell-microenvironment interactions and intracellular damage response processes in both TNBC and NTNBC but with different co-expression patterns between the subtypes; (iii) substantially more neural functions are utilized in TNBC than in NTNBC; (iv) genes involved in neural crest development and neurotransmitter secretion are predicted to regulate adaptive immunity and cell cycle only in TNBC, while genes relevant to glia development seem to promote both innate and adaptive immunity, as well as cell cycle regulation in NTNBC
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