Study Of Toll-like Receptors Expression In Breast Cancer And Toll-like Receptors Gene Polymorphisms In Breast Cancer Of Qingdao

Background and objective:Toll-like receptors (TLRs) were identified as transmembrane signal transduction proteins in recent years. As a group of pattern recognition receptors (prrs), TLRs play important roles in the innate immunity by recognizing pathogen associated molecular patterns (PAMPs) and further modulate adaptive immune system. PAMPs trigger TLR signaling cascades, leading to the release of proinflammatory cytokines, and play critical roles in infectious diseases. TLRs were recently shown to be expressed by cancer cells, and that indicate TLRS also play an important role in the initiation and progression of cancer. TLR activation may be an important event in tumor cell immune evasion. TLRs gene polymorphisms have been related to increased susceptibility to cancer developmentment in various organs. However, the expression and gene polymorphisms of TLRs in breast cancer specimens have few characterized. The aim of this study was to investigate the expression and clinical relevance of TLR2,3,4and9in breast cancer and evaluated the possible association between TLR2(-196to-174del), TLR3(c.1377C/T), TLR4Asp299Gly, TLR4Thr399Ile, TLR9(1486T/C) and TLR9(C2848T) gene polymorphisms and breast cancer in Qingdao.Method①The TLRs expression of213cases of breast cancer and its adjacent tissues were detected with RT-PCR and real-time PCR, and the relationship between TLRs and clinicopathological features of breast cancer were analyzed.②Peripheral blood samples were collected from213histopathologically confirmd breast cancer patients and200cancer-free, age-matched healthy femal controls from Qingdao. Genomic DNA was extracted and genotyped for TLR2,3,4and9uing polymerase chain reation-based restriction fragment length polymorphism (PCR-RFLP). Genotyp of some samples were analyzed by PCR and sequencing. The allelic and genotypic frequencies of TLRs SNPs were compared between patients and controls in a case-control study.Results①a. The TLRs expression in breast cancer tissues was significantly higher than that in adjacent tissues (p<0.05). Expression of TLR2increased gradually with histological grade and the status of ER(+), PR(+) and p53gene(-)(P<0.05), but it had no correlation with the progress of T stages and N stages. Expression of TLR3increased gradually with histological grade, the progress of T stages and the status of p53gene(+)(P<0.05). but it had no correlation with the progress of N stages and the status of ER(+) and PR(+). Expression of TLR4increased gradually with histological grade, the progress of T stages and the status of ER(+) and PR(+)(P<0.05), but it had no correlation with the progress of N stages and the status of p53gene(+). Expression of TLR9showed no correlation with the all clinicopathological features.b. Tumors showed higher expression levels of TLRs than that in adjacent tissues (p<0.05)(2)a. As far as (-174to-196) in TLR2gene ins/del and del/del genotypes and del allele were significantly more frequent in breast cancer patients compared to healthy controls.b. No significant difference of (c.1377C/T) genotypes and allele frequency was found between in breast cancer patients and healthy controls.c. No TLR4Asp299Gly and TLR4Thr399Ile mutant genotype was detected in any breast cancer patients and healthy controls.d. No significant difference of TLR91486T/C genotypes was found between in breast cancer patients and healthy controls, but the c allele frequency showed borderline significance(P=0.053, OR=1.317,95%CI=0.997-1.739). No’significant difference of TLR9C2848T genotypes and allele frequency was found between in breast cancer patients and healthy controls.Conclusions①LRs overexpressed in breast cancer. TLRs may represent therapeu-tic targets in breast cancer.②(-174to-196del) of TLR2gene polymorphisms may confer an increased susceptibility to breast cancer development in Qingdao. However, the assosication between TLR91486T/C gene polymorphisms and susceptibility of breast cancer in Qingdao was uncertainty, and We should continue to survey it using appropriate way and larger samples.