| Background:Esophageal cancer is one of the most common digestive malignant tumor in the world. The mortality rate of esophageal cancer in China accounts for about 25 percent of the annual death from cancer in China. The 5-year survival rate is less than 15%, ranking position 4 of cancer death. Now, the study of pathogeny of esophageal cancer has founded that except for smoking, alcohol, lack of trace elements and nitrite, nitrosamines factors, biological pathogens such as h. pylori (HP) chronic infection causes a persistent inflammation and the long-term reflux of gastric acid and bile causes chronic injury also has an important influence in the formation of esophageal cancer. Lots of study confirms that the relationship between inflammation and tumor is very close. The mechanism may be like this: when the body experience the wound repair or pathogens invasion, the immune system will be activated and recruiting large number of inflammatory cells to the injury parts, and then the cells will secrete all kinds of cytokines (including inflammatory factor, chemotactic factors, adhesion molecule), form a new microenvironment with the extracellular matrix. In the microenvironment, the sustaining existence of cytokines and chemotactic factors combine the cascade reaction induce cell proliferation. And the long-term existence of inflammatory mediators increase the production of ROS eventually leading to DNA damage. Cells with DNA damage keep on propagating incontrollable in the microenvironment form by inflammatory cells and many biological factors, which eventually led to the procedure of cancer. Current research found that TLRs (like receptors) mediated signaling pathways plays an important role in tumor formation process. When TLRs bone with corresponding ligand, the classic NF - k B signaling pathways will be actived, and then produce various cytokine forming the microenvironment for tumor growth, and promote the development of cancer eventually.Toll like receptors are the immune receptors which be found in recent years, it plays an important role in identifying pathogens in the body's immune defenses.TLR4 is the first TLR related proteins found by human, which has closer relationship with the causes of cancer than other family members. The main ligand of TLR4 is gram-negative bacteria LPS endotoxin/cell components.TLR4 also has A lot of endogenous ligands, such as respiratory syncytial virus protein F, mycobacteria composition, heat shock protein, saturated and unsaturated fatty acids, hyaluronic acid clips, surface active protein A etc. The TLR4 signal transmission pathway belongs to the classic MyD88 depended signal transmission pathway, which can active NF -κB signaling pathways and stress kinase pathway. And then start the gene transcription of inflammation factors,(including TNF-a, IL-1, IL-6 and IL-8, etc) which will release a lot of cytokines and chemotactic factors. Large study reports that TLR4 and NF-KBp65 have a positive expression in gastrointestinal tumor tissue such as gastric cancer, colorectal cancer, pancreatic cancer and liver cancer. But there are little related researches and reports about whether it also has expression in esophageal organization and its significance.Objective:This experiment aimed at discuss the expression of TLR4 and the key factor of the signal transmission pathway—NF-κBp65 in esophageal organization from protein lever, and analysised the correlation among TLR4, NF - k B p65 and Clinicopathologic data such as tumor cell differentiation degree, lymph node metastasis. Evaluated whether the TLR4—NF-KBp65 signaling transmission pathways was link to the esophageal tumor development and progression, as well as discussed its clinical significance.Method:The expression of TLR4 and NF-κBp65 in 30 cases of esophageal squamous cell carcinoma tissues and 20 cases of normal esophageal mucosal tissues were detected by Envision two-step immunohistochemical method.We observed their expression to explore the mutual relationship between the positive expression and the Clinicopathologic data of tumor. All the specimens were confirmed by pathology for esophageal squamous cell carcinoma or esophageal normal tissue. Data were performed with SPSS 13.0 software. Chi-square test and Spearman rank correlation were used, All material difference are expressed in P, and Statistical significant level was considered as a=0.05, P<0.05 was considered significant. Result:1,The positive expression rate of TLR4 in Esophageal cancer organizations and normal esophageal mucosal tissues were 43.3% (13/30), 10% (2/20) respectively; The positive expression rate of NF-κBp65 in Esophageal cancer organizations and normal esophageal mucosal tissues were 17% (56.7% / 30), 25% (5/20) respectively.2,The positive expression rate of TLR4 and NF-κBp65 in Esophageal cancer organizations were significantly higher than those in normal esophageal mucosal tissue, the positive expression rate was statistically significant difference.3,In addition, the positive expression rate of TLR4 and NF-κBp65 in Esophageal cancer organizations has nothing to do with the age, sex and tumor location (P > 0.05).4,The positive expression rate of TLR4 and NF-κBp65 in Esophageal cancer organizations were related to the tumor differentiation degree. The tumor with lower histological grade was expressed higher level of TLR4 and NF-κBp65. The correlation coefficient of TLR4 and tumor differentiation degree was r = - 0.522 (P - 0.003) .The correlation coefficient of NF-κp65 and tumor differentiation degree was r=-0.522(P = 0.005).5,The positive expression rate of NF-κBp65 was also related to lymph node metastasis. The expression rate of NF-κBp65 with lymph node metastasis was higher than those with no transfer (X=5.436, P < 0.05).6,We also found that the correlation of the positive expression rate of TLR4 and NF-κBp65 in Esophageal cancer organizations was positive, (r = 0.426, P = 0.019).Conclusion:1,There is a high level expression of TLR4 and NF-κBp65 in Esophageal cancer organizations. And both of the expression were negatively correlated with the differentiation degree of esophageal cancer. It shows that TLR4 and NF-κBp65 were not only play an important role in the development and occurrence of esophageal cancer, but also have particular concern with grade malignancy of cancer. In addition, the expression of NF-κBp65 was related to lymph node metastasis, and it shows that NF-κBp65 have certain effect in tumor metastasis.2,The intensity expressions of TLR4 and were positively related, it indicated that there could existed some kinds of dependency between TLR4 and NF-KBp65 in promoting the occurrence of esophageal cancer. The intensive study of its molecular pathways may help to provide some new targets of the treatment in esophageal cancer。...
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