TLR4/NF-κB信号通路分子在胃癌中的表达及其与胃癌临床病理特征的相关性

Expressions of Molecules in TLR4/NF-κB Signaling Pathway and Their Correlations With Clinicopathological Characteristics of Gastric Cancer

背景:TLR4/NF-κB信号通路可通过多种机制参与恶性肿瘤的发生,然而关于其在胃癌中作用的研究较少。目的:探讨胃癌组织中TLR4/NF-κB信号通路相关分子表达情况及其与胃癌临床病理特征的关系。方法:收集第四军医大学西京消化病医院2014年1月—2016年10月内镜活检和外科手术切除胃癌病理标本154例,按有无幽门螺杆菌(Hp)感染分为Hp阳性组和Hp阴性组,以real-time PCR检测胃癌组织中的TLR4、My D88、NF-κB mRNA表达。结果:Hp阳性组胃癌组织中的TLR4、My D88、NF-κB mRNA表达均显著高于Hp阴性组(P<0.05);低-未分化、有远处转移、TNM分期Ⅲ、Ⅳ期病例胃癌组织中的TLR4、My D88、NF-κB mRNA表达分别显著高于高-中分化、无远处转移和TNM分期Ⅰ、Ⅱ期者(P均<0.05)。Spearman相关系数分析显示,TLR4、My D88、NF-κB mRNA在胃癌组织中的表达水平两两之间呈显著正相关(TLR4与My D88:r=0.734,TLR4与NF-κB:r=0.657,My D88与NF-κB,r=0.828,P均<0.05)。结论:TLR4/NF-κB信号通路与Hp感染相关胃癌的发生有密切联系。胃癌组织中TLR4/NF-κB信号通路相关分子表达与肿瘤恶性行为显著相关,该信号通路可能是胃癌进展的重要机制之一。

Background: TLR4/NF-κB signaling pathway is involved in the tumorigenesis of a variety of malignancies via multiple mechanisms. However,its role in gastric cancer is not clearly clarified yet. Aims: To investigate the expressions of molecules in TLR4/NF-κB signaling pathway and their correlations with the clinicopathological characteristics of gastric cancer. Methods: A total of 154 endoscopic or surgical specimens of gastric cancer were collected at the Xijing Hospital of Digestive Diseases,the Fourth Military Medical University from Jan. 2014 to Oct. 2016 and were categorized into Helicobacter pylori( Hp)-positive group and Hp-negative group according to the status of Hp infection. Expressions of TLR4,My D88 and NF-κB mRNA in gastric cancer tissues were detected by real-time PCR. Results: In Hp-positive group,expression levels of TLR4,My D88 and NF-κB mRNA in gastric cancer tissues were significantly higher than those in Hp-negative group( P < 0. 05). Furthermore,it was found that the expression levels of TLR4,My D88 and NF-κB mRNA in patients with poorly differentiated or undifferentiated cancer,with distant metastasis and in TNM stage Ⅲ-Ⅳ were significantly higher than those in patients with well-to-moderately differentiated cancer,without distant metastasis and in TNM stage Ⅰ-Ⅱ,respectively( P all < 0. 05). Spearman correlation coefficient analysis revealed that the expression levels of TLR4,My D88 and NF-κB mRNA were positively correlated with each other in gastric cancer tissues( r = 0. 734 for TLR4 and My D88,r = 0. 657 for TLR4 and NF-κB,and r = 0. 828 for My D88 and NF-κB,P all < 0. 05).Conclusions: TLR4/NF-κB signaling pathway is implicated in the tumorigenesis of Hp infection-related gastric cancer. In gastric cancer tissues,TLR4/NF-κB signaling pathway might be associated with the malignant behavior of tumor and promote tumor progression.