Many epidemiological reports have indicated an increase in the incidence of
breast cancer among psychotic patients, suggesting that the targets of
antipsychotics,
neurotransmitter receptors, may have a role in
tumorigenesis. However, the functions of
neurotransmitter receptors in
cancer are barely known. Here, we analyzed 44
neurotransmitter receptors in
breast cancer and revealed that the expression of 34 receptors was positively correlated with relapse-free survival rates (RFS) of patients using the public database (n = 3951). Among all these receptors, we revealed decreased expression of HTR6 in human advanced
breast cancer versus
tumors in situ using our original data (n = 44). After a pan-
cancer analysis including 22
cancers (n = 11262), we disclosed that HTR6 was expressed in 12
tumors and uncovered its influence on survival in seven
tumors. Using multi-omics datasets from Linkedomics, we revealed a potential regulatory role of HTR6 in MAPK, JUN, and leukocyte-differentiation pathways through enriching 294 co-expressed phosphorylated
proteins of HTR6. Furthermore, we proclaimed a close association of HTR6 expression with the immune microenvironment. Finally, we uncovered two possible reasons for HTR6 down-regulation in
breast cancer, including deep deletion in the genome and the up-regulation of FOXA1 in
breast cancer, which was a potential negatively regulatory
transcription factor of HTR6. Taken together, we revealed a new function of
neurotransmitter receptors in
breast cancer and identified HTR6 as a survival-related gene potentially regulating the immune microenvironment. The findings in our study would improve our understanding of the pathogenesis of
breast cancer and provided a theoretical basis for personalized medication in psychotic patients.