Hp感染性胃癌患者外周血单核细胞TLR4/MyD88/NF-κB信号通路的变化及其临床意义

Clinical significance of changes of TLR4/MyD88/NF-κB signaling pathway in peripheral blood mononuclear cells of gastric cancer patients with Helicobacter pylori infection

背景幽门螺杆菌(Helicobacter pylori,H.pylori)与胃癌的相关性已经得到了世界范围内的普遍认可,而TLR4/MyD88/NF-κB信号通路相关因子在胃癌患者中明显存在异常表达,因此与胃癌的发生及发展存在密切关系,但其是否与胃癌患者H.pylori感染之间也存在相关性,临床相关研究较少,值得进一步研究.目的探究H.pylori感染性胃癌患者外周血单核细胞TLR4/MyD88/NF-κB信号通路的变化及其临床意义.方法选取2017-10/2020-10于湖州市第三人民医院收治的80例胃癌患者作为研究组,另外选择同期来我院进行体检且体检结果合格的50例健康者作为对照组.比较两组受试者、不同病理特征胃癌患者以及胃癌H.pylori感染患者外周血单核细胞中TLR-4、核因子κB(NF-κB)和髓样分化因子(MyD88)蛋白表达水平,并分析胃癌患者TLR-4、NF-κB和MyD88蛋白水平与H.pylori感染的相关性.结果与对照组相比较,研究组TLR-4、NF-κB、MyD88表达均明显偏高,差异均有统计学意义(P<0.05);胃癌患者不同临床分期、是否出现淋巴结转移和不同浸润深度的TLR4/MyD88/NF-κB信号通路相关分子表达比较,差异均有统计学意义(P<0.05);而不同性别、年龄的TLR4/MyD88/NF-κB信号通路相关分子表达比较,差异无统计学意义(P>0.05);与H.pylori感染阴性相比较,H.pylori感染阳性TLR-4、NF-κB、MyD88表达均明显偏高,差异均有统计学意义(P<0.05);Pearson检验发现,H.pylori感染与TLR-4、NF-κB、MyD88表达之间有正相关(r=0.726、0.684、0.631,P<0.01).结论胃癌患者外周血单核细胞中的TLR4/MyD88/NF-κB信号通路相关分子表达水平均显著升高,且不同病理特征及参数分组下的TLR4/MyD88/NF-κB信号通路相关分子表达水平存在显著差异,推测H.pylori感染可能通过诱发TLR4/MyD88/NF-κB信号通路异常表达参与了胃癌的发生及发展.

BACKGROUND The correlation between Helicobacter pylori(H.pylori)and gastric cancer has been widely recognized in the world.The abnormal expression of TLR4/MyD88/NF-κB signaling pathway related factors is obvious in gastric cancer patients,suggesting that this pathway is closely related to the occurrence and development of gastric cancer.However,there is also a correlation between the TLR4/MyD88/NF-κB signaling pathway and H.pylori infection in gastric cancer patients.AIM To investigate the clinical significance of changes of the TLR4/MyD88/NF-κB signaling pathway in peripheral blood mononuclear cells(PBMCs)of patients with gastric cancer infected by H.pylori.METHODS Eighty gastric cancer patients treated at Huzhou Third People’s Hospital from October 2017 to October 2020 were selected as a study group,and 50 healthy ts volunteers were selected as a control group.The expression levels of TLR-4,NF-κB,and myeloid differentiation factor(MyD88)in PBMCs of gastric cancer patients with different pathological characteristics and H.pylori infection status were compared between the two groups,and the correlation between TLR-4,NF-κB,and MyD88 protein levels and H.pylori infection was analyzed.RESULTS Compared with the control group,the expression levels of TLR-4,NF-κB,and MyD88 in the study group were significantly higher than those of the control group(P<0.05).The expression of TLR4/MyD88/NF-κB signaling pathway related molecules differed significantly in gastric cancer patients with different clinical stages,lymph node metastasis status,and depth of invasion(P<0.05),and TLR4/MyD88/NF-κB expression differed significantly in different gender and age groups(P<0.05).The expression of TLR-4,NF-κB,and MyD88 in the H.pylori positive group was significantly higher than that of the H.pylori negative group(P<0.05).Pearson analysis showed that H.pylori infection was positively correlated with the expression of TLR-4,NF-κB,and MyD88(r=0.726,0.684,and 0.631,P<0.01).CONCLUSION The expression levels of TLR4/MyD88/NF-κB signaling pathway related molecules in peripheral blood mononuclear cells(PBMCs)of patients with gastric cancer increase significantly,and are significantly different among groups with different pathological characteristics and parameters.It is speculated that H.pylori infection may participate in the occurrence and development of gastric cancer by inducing the abnormal expression of the TLR4/MyD88/NF-κB signaling pathway.