具核梭杆菌诱导葡萄糖转运蛋白4高表达在食管鳞癌组织中的临床意义及预后价值

Clinical Significance and Prognostic Value of the High Expression of Glucose Transporter 4 Induced by Fusobacterium Nucleatum in Esophageal Squamous Cell Carcinoma

【目的】分析食管鳞癌患者癌组织中具核梭杆菌(Fn)对葡萄糖转运蛋白4(GLUT4)的诱导效应与临床病理特征及5年生存期的相关性,并探讨其临床意义及预后价值。【方法】选择2014年1月到2015年3月安阳肿瘤医院手术切除的96例食管鳞癌患者癌组织石蜡包埋标本为研究对象,采用RNAscope及免疫组织化学方法分别检测食管鳞癌癌组织中Fn感染及GLUT4的表达情况,并分析Fn对GLUT4的诱导效应,及其与临床病理特征相关性;采用Kaplan-Meier生存分析法绘制生存曲线并利用Log-rank检验方法分析Fn对GLUT4的诱导效应与生存时间之间相关性。【结果】食管鳞癌中可见癌细胞胞浆出现红色颗粒,为Fn感染阳性,连续切片癌细胞浆膜出现棕黄色颗粒,为GLUT4表达阳性;且Fn感染与其表达具有显著一致性(P<0.05)。同时Fn诱导GLUT4表达阳性组与性别、吸烟、饮酒、分化程度、浸润深度、淋巴结转移及临床分期显著相关(P<0.05)。且阳性组5年生存率及中位生存时间均明显低于阴性组(P<0.05)。【结论】长期吸烟、饮酒会导致恶劣的口腔环境,Fn更容易在这种环境下感染并定植,从而诱导癌细胞GLUT4高表达,增强葡萄糖代谢,促进食管鳞癌恶性进展。有效清除Fn并抑制癌细胞GLUT4表达可能为食管鳞癌治疗提供新策略和治疗手段。

【Objective】To analyze the induction of glucose transporter 4(GLUT4)by Fusobacterium nucleatum(Fn)in esophageal squamous cell carcinoma(ESCC)and its correlation with clinicopathologic features and 5-year survival,and to explore its clinical significance and prognostic value.【Methods】Paraffin-embedded specimens of esophageal squa⁃mous cell carcinoma were collected from 96 patients with this disease from January 2014 to March 2015 at Anyang Cancer Hospital.RNAscope and immunohistochemistry were used to detect the expression of Fn and GLUT4 in Esophageal squa⁃mous cell carcinoma tissues,and to analyze the induced effect of Fn on GLUT4 and its correlation with clinicopathologic features.Survival curves were drawn by Kaplan-Meier survival analysis and correlation between GLUT4-induced effect of Fn and survival time was analyzed by Log-rank test.【Results】There were red granules in the cytoplasm of ESCC,which were positive for Fn infection,brown granules in the plasma membrane of ESCC were positive for GLUT4 expression,and the expression of GLUT4 was consistent with the Fn infection(P<0.05).At the same time,the positive expression of GLUT4 induced by Fn was significantly correlated with gender,smoking,drinking,degree of differentiation,depth of invasion,lymph node metastasis and clinical stage(P<0.05).The 5-year survival rate and median survival time in the positive group were significantly lower than those in the negative group(P<0.05).【Conclusions】Long-term smoking and drinking will lead to bad oral environment.Fn is more easily infected and planted in this environment,which can induce the high expression of GLUT4 in plasma membrane of cancer cells,enhance glucose metabolism,and promote the malignant progression of ESCC.Effective removal of Fn and inhibition of GLUT4 expression may provide a new strategy and effective treatment for esophageal squamous cell carcinoma.