Expression Profile Of Innate Immune Pattern Recognition Receptors In Human Breast Cancer

Cancer has been a major health problem of all the world. In female, breast cancer has become the first in incidence and the second highest in lethality. More and more research focused on trying to clarify the connection between the disorder of immune system and tumor genesis. PRRs(pattern recognition receptors) are the fundamental component of the immune system, which are proteins expressed by innate immune cells to recognize the PAMPs and DAMPs. Part of the PRRs are expressed at the membrane of cells, TLRs, for example, while others expressed inside of cell, such as RLRs and NLRs. Increasing number of evidence proved that the tumor genesis of breast cancer may link to PRRs.So we obtained the expression data and clinic data of 1215 breast cancer case from TCGA database and attempted to analyze the expression pattern of TLRs, RLRs and NLRs in various aspects, including in tumor and normal tissue, different PAM50 subtypes, different stages, TP53 mutation. At the same time, we divided patients into two groups to carry on the overall survival analysis and estimated the prognosis, according to the expression level of high or low. KaplanMeier method were used to estimate the difference between the two groups. At last, we checked nine cytokines which are the downstream effect molecules of TLRs, RLRs and NLRs signal pathways in tumor and normal tissue, various grades and stages, TP53 mutant and wild type cases and tried to establish the connection between the variation of cytokines expression and the profile of PRRs expression.In breast cancer, we found that there were three pattern of the expression of PRRs, upregulated, down-regulated or no statistical difference. At the same time, we also observed that analysis data from different sources, different databases, for example, can result some discrepancy of expression level.For all TLRs, almost all of the expression of TLRs showed a lower level in tumor tissue rather than the normal tissue except three no significant genes. For RLRs, all RLRs were unregulated in tumor tissue. For NLRs, the expression of NLRP1, NLRP3, NLRP10, NLRX1, and NOD1 reduced in tumor tissue, while NLRP7, NLRP12, NOD2 increased.As compared with a high level of m RNA expression, a low level of m RNA expression was strongly associated with HER2-Enriched breast tumors, such as TLR3, TLR5, RLR3, NLRP6, and NAIP. In contrast, for TLR6, TLR8, TLR9, NLRC5, NOD1, as compared with a low level of m RNA expression, a high level of m RNA expression was strongly associated with HER2-Enriched breast tumors. When compared with high level of TLR3, RLR3, NLRP6, NAIP m RNA expression, a low level expression of was associated with TNBC. Conversely, a higher expression of TLR5, TLR6, TLR8, TLR9, NLRC5 and NOD1 was related to TNBC. The condition of Lum A/B was as a reference. Generally, TNBC was considered as the worst type, then HER2-Enriched subtype, and the Luminal A/B. In the analysis of TLR3 and TLR4, the expression level decreased with the degrees of subtype and showed a strong associated with malignant degrees. But some of the TLRs do not follow the rules, for example, TLR1 and TLR2 showed no significance in the normal tissue and the TNBC tissue, but in the other two subtypes. And for TLR6 and TLR7, there was no significance in the normal tissue and tumor tissue, but increased when compared with only TNBC subtype. The expression of RLR2 showed a positive correlation with malignant degrees. The expression of RLRs increased in Lum A/B rather than in ER-/PR- breast tumor.We thought the TP53 mutation mean a worst condition of breast cancer. The expression of TLR1, TLR2, TLR6, TLR8, TLR9, RLR2, NLRP7, NLRP10, NLRC4, NLRC5, NOD1, and NOD2 were higher than TP53 wild type. But the expression of TLR3, TLR5, RLR3, NLRP6, NLRP12, NAIP, were just the opposite.After the survival analysis, TLR4, TLR7, NLRP4, NLRP7 showed the statistical differences in overall survival. The higher expression of TLR4/TLR7 means a worse prognosis, and the NLRP4/NLRP7 was just the opposite. The rest if the PRRs showed no significant difference. The profile of TLR3, TLR9, RLR2, NLRP6, NLRP7, and NOD2 showed strong correlations to the clinic characters and prognosis. This may contribute to the research of pathogenesis and progression of breast cancer.By researching the expression pattern of 26 PRRs, we found that most of the PRRs showed differences in tumor tissue, PAM50 subtypes, different stages and TP53 mutation, and the regulation is crucial to the processing and prognosis of breast cancer. We hoped this research may have value to the identification of molecular targets and clinic therapies.