The Expression And Clinical Significance Of TLR9-NF-κB Signaling Pathway In Human Gastric Cancer Tissue

Objective:To investigated the expressions of Toll-like receptor-9(TLR9) and nuclear factor-KB (NF-κB) protein in human gastric cancer tissue and adjacent normal tissue.To explore the effect of TLR9-NF-κB signaling pathway on the pathogenesis of gastric carcinoma and effect on gastric progression、invasion and metastasis and provide early diagnosis and a new thinking and scientific basis to the targeting therapy of gastric cancer.Methods:The expressions of TLR9and NF-κB protein were tested by immunohistochemical techinique (SP three-steps method)in102cases of gastric carcinoma which were confirmed by pathological results and30cases of adjacent normal tissue. The relationship between expressions and age、sex、lesion size、lesion location、histology type、degree of histodifferentiation、depth of invasion、clinical stages and lymphatic metastasis were also analyzed. The results of detection were analyzed with t or χ2test, and then the relationship between the expressions of TLR9and NF-κB were analyzed with Spearman correlation analysis.Result:The positive rates of TLR9and NF-κB in gastric carcinoma were significantly higher than adjacent normal tissue, the positive rates of TLR9and NF-κB in tumor were76.5%and80.4%whereas in adjacent normal tissue were36.7%and33.3%and the difference had statistically significant(P<0.05).The expressions of TLR9and NF-κB in poorly differentiated carcinoma were significantly higher than in moderately-well differentiated carcinoma, the positive rates of TLR9and NF-κB in poorly differentiated carcinoma were80.6%and87.1%whereas in moderately-well differentiated carcinoma were64.5%and64.5%and the difference of NF-κB had statistically significant(P<0.05). The expressions of TLR9and NF-κB in which have broken through serosa were significantly higher than in which haven’t broken through serosa, the positive rates of TLR9and NF-κB in which have broken through serosa were94.6%and89.2%whereas in which haven’t broken through serosa were59.1%and70.5%and the difference had statistically significant(P<0.05). The expressions of TLR9and NF-κB in which have lymphatic metastasis were significantly higher than in which have no lymphatic metastasis, the positive rates of TLR9and NF-κB in which have lymphatic metastasis were90.4%and86.5%whereas in which have no lymphatic metastasis were48.3%and65.5%and the difference had statistically significant(P<0.05). The positive rate of TLR9in male and female were72.4%and81.8%whereas the rate of NF-κB is79.3%and81.8%. The positive rate of TLR9in people(age≥60) and people(age<60)were78.0%and74.4%whereas the rate of NF-κB is83.1%and76.7%. The positive rate of TLR9in tumor (size≥5cm) and tumor (size<5cm) were78.7%and74.5%whereas the rate of NF-κB is78.7%and81.8%. The positive rate of TLR9in fundus-body、lesser curvature and sinuses ventriculi were86.2%、75.8%and70.0%whereas the rate of NF-κB is86.2%、81.8%and75.0%. The positive rate of TLR9on Ⅰ+Ⅱ clinical stage and Ⅲ+Ⅳ clinical stage were62.3%and91.7%and the difference had statistically significant(P<0.05) whereas the rate of NF-κB is77.8%and80.6%. The positive rate of TLR9in adenocarcinoma and signet ring cell carcinoma were75.9%and78.9%whereas the rate of NF-κB is83.1%and68.4%. There was no statistical difference in the age、sex、 lesion size、lesion location and histology type about the expressions of TLR9and NF-κB. The expression of TLR9was positively correlated with NF-κB in gastric cancer tissue (r=0.513, P<0.001)Conclusion:The expressions of TLR9and NF-κB in gastric cancer tissue were significantly higher than in adjacent normal tissue.Over-expression of TLR9and NF-κB were positively correlated with the degree of histodifferentiation、depth of invasion and lymphatic metastasis. The expressions of two proteins have correlation. The high expression of TLR9possibly initiate the activation of NF-κB via MyD88-dependent signaling pathway and then initiate the activation and transcription of downstream controlled gene and finally affected the gastric progression、invasion and metastasis with the effects of anti-apoptosis、promoting the form of tumor vascellum and degrading the extracellular stroma and basement membrane.