The Expression And Significance Of TLR4, NF-κB And NLRP3 In Gastric Cancer Tissues

Research background and objective:TLR4 is a type of pattern recognition receptors（PRRs）,which is highly homologous and singular.It can further promote the activation of NF-κB by identifying the pathogenassociated molecular patterns（PAMPs）and activating the corresponding signal transduction pathway.Now,the research has shown that TLR4 expressed highly on a variety of malignant tumors,which can promotes the proliferation of malignant tumors,inhibits tumor cells apoptosis,and induces tumor immune evasion,etc^[1-3].NF-κB is a heterodimer composed of NF-κB1 and RealA,which is mainly involved in physiological processes such as inflammation,cell proliferation and differentiation,However,if the persistent abnormal activation of NF-κB,it can also be involved in the invasion and metastasis of tumor cells^[4-5].With the gradual progress of research,some researches have confirmed that abnormal TLR4/NF-κB signaling pathway may induce malignant transformation of gastric mucosal epithelial and promote the progress of gastric cancer.NLRP3 inflammasome,which is a type of well-researched and complex inflammasome,can induce the release of a large number of inflammatory cytokines by stimulating caspase-1 activation that triggers the secretion of pro-inflammatory cytokines,including interleukin-1βand interleukin-18.At the same time,the overexpression of interleukin-1βand interleukin-18 plays an important role in tumor progression^[6-7].According to the current domestic and foreign literature reports,NLRP3inflammasome plays a central role in bladder cancer,nasopharyngeal carcinoma or other malignant tumors.However,there is a lack of literature on the study of NLRP3 inflammasome in gastric cancer.Therefore,in this experimental study,we will use the immunohistochemical method in this experimental,testing the expression of TLR4,NF-κB and NLRP3 in gastric cancer tissues and in paracancerous tissues,to analyze whether there is correlation between tumor size,tissue differentiation,tumor stage,distant metastasis of gastric cancer with them,and discusse whether there is a correlation between them,so that we can clear the pathogenesis of gastric cancer,and provide a new direction for treating stomach cancer.Methods:In this study,We randomly selected 42 patients that have received surgical treatment and pathology diagnosed of stomach cancer from January 2014 to December 2017 in Department of gastrointestinal surgery,affiliated hospital of southwest medical university.All specimens have complete clinical data,and none of them received radiotherapy,chemotherapy,immunotherapy or other therapy before the operation.we selected cancer tissues and paracancerous tissues（The pathology confirmed normal tissue）at the department.We analysis the expression of TLR4、NF-κB and NLRP3 in gastric cancer tissues and in paracancerous tissues respectively,the correlation between the expression of them in gastric cancer tissues through statistical software.Results:1.The positive expression rates of TLR4,NF-κB and NLRP3 were69.05%、71.43%、78.57%respectively in gastric cancer tissues.The positive expression rates of TLR4,NF-κB and NLRP3 were 11.90%,23.81%and 16.67%respectively in paracancerous tissues.Therefore,The positive expression rates of TLR4,NF-κB and NLRP3 in gastric cancer tissues was significantly higher than the paracancerous tissues,and the difference was statistically significant（P<0.05）.2.In terms of clinicopathological features,The positive expressions of TLR4,NF-κB and NLRP3 in gastric cancer tissues have closely relate with lymph node metastasis and clinical TNM staging.In the gastric cancer tissues with lymph node metastasis,the positive expression of TLR4,NF-κB and NLRP3 were higher,and the difference was statistically significant（P<0.05）.Meanwhile,in the clinical TNM stages,the proportion of patients belong to III/IV stage was higher in the positive expressions of TLR4,NF-κB and NLRP3,and the difference was statistically significant（P<0.05）.However,the expression of TLR4,NF-κB and NLRP3 have no significant difference in gender,age,tumor size,tissue differentiation,vascular/nerve invasion or other aspects（P>0.05）.3.Spearman rank correlation analysis showed that the expression of TLR4、NF-κB and NLRP3 in gastric cancer tissues were positively correlated（P<0.05）.4.The positive expressions of TLR4,NF-κB and NLRP3 in gastric cancer tissues have closely relate with distant metastasis（P<0.05）,However,there was no significant difference in expression with preoperative pyloric obstruction（with/without）,anemia（with/without）,AFP（<10ng/ml or≥10ng/ml）,CEA（<6ng/ml or≥6ng/ml）and CA199（<37IU/ml or≥37IU/ml）（P>0.05）.Conclusion:1.The positive expressions of TLR4,NF-κB and NLRP3 in the gastric cancer tissues were higher than that in the paracancerous tissues.2.The expression of TLR4,NF-κB and NLRP3 in gastric cancer tissues is correlated with lymph node metastasis,TNM staging and distant metastasis,these date suggest that all of them may be involved in the proliferation,invasion and metastasis of gastric cancer.3.The expression of TLR4,NF-κB and NLRP3 was positively correlated in gastric cancer tissues,which indicated that the high expression of TLR4 in gastric cancer tissues promoted the up-regulation of NF-kB and NLRP3.Among of them may play a synergistic role in promoting the development and progression of gastric cancer.