Expression Of NRAGE And ?-catenin In Esophageal Squamous Cell Carcinoma And Its Relationship With Radiotherapy Effect

Objective:It is a high incidence and high mortality of esophageal cancer in china.Radiation resistance from tumor cells is one of the main causes of treatment failure.Our previous studies have found that NRAGE may be involved in the formation of radiation resistance of esophageal squamous cell carcinoma by regulating the nuclear transfer of?-catenin and relying on Wnt/?-catenin signaling pathway.But this conclusion just is the result from the cell level,the correlation between NRAGE and?-catenin in patients'internal state and whether they are related to the radiotherapy of esophageal cancer have not been reported.In this study,immunohistochemical stain was used to analyze the expression levels of NRAGE and?-catenin of the patients with esophageal squamous cell carcinoma.And then to further verify the correlation between the two genes and its relationship with radiotherapy effect.Methods:Immunohistochemical method was used to evaluate the expression of NRAGE and?-catenin in 44 patients with esophageal squamous cell carcinoma.The clinical data of 44 patients were statistically analyzed by rank sum test,chi-square test,log-rank test and Cox proportional risk regres-sion model.Results:1.The radiotherapy of 44 patients with esophageal cancer was effective in 36 cases(CR+PR),and 8 cases(NR)were ineffective in radiotherapy.The survival rate of the effective group was significantly higher than that in the invalid group.Survival rates were statistically significant in both groups(?~2=14.831,P<0.001).The 3-year survival rate of the 44 patients was 36%,and the 5-year survival rate was 21%.The 3-year survival rate of the effective group was 45%,and the 5-year survival rate was 26%..The 3-year survival rate of the invalid group was 0%,and the 5-year survival rate was 0%.2.The general expression level of NRAGE protein in esophageal squamous cell carcinoma was negatively correlated with the short-term efficacy(Z=-2.240,P=0.025),compared with the effective group,NRAGE was highly expressed in the invalid group and had statistical significance(P=0.0162).and was not related to age(P=0.651),sex(P=0.729),clinical stage(P=0.930),lesion length(P=0.139)and lymphatic metastasis(P=0.151).The nuclear expression level of NRAGE protein in esophageal squamous cell carcinoma was negatively correlated with the short-term efficacy(Z=-2.653,P=0.008),compared with the effective group,NRAGE was highly expressed in the invalid group and had statistical significance(P=0.0034).And it was not related to age(P=0.271),sex(P=0.271),clinical stage(P=0.755),lesion length(P=0.612)and lymphatic metastasis(P=0.146).At the general expression of NRAGE,there was no statistical significance difference on the long-term survival rate between the strong positive group and the positive and weakly positive group(P=0.198).As for NRAGE nuclear expression,the long-term survival rate in the positive group and weakly positive group was lower than that in the strong positive group,and it has statistical significance(P<0.001)3.The general expression level of?-catenin protein in esophageal squamous cell carcinoma was not correlated with the short-term efficacy(Z=-1.473,P=0.141).compared with the effective group,there was no statis-tical significance difference on the general expression level of?-catenin in the invalid group(P=0.0838),and it also was not related to age(P=0.283),sex(P=1.000),clinical stage(P=0.821),lesion length(P=0.391)and lymphatic metastasis(P=0.217).The nuclear expression level of?-catenin protein in esophageal squamous cell carcinoma was negatively correlated with the short-term efficacy(Z=-2.692,P=0.007).compared with the effective group,the nuclear expression level of?-catenin was highly expressed in the invalid group and had statistical significance(P<0.001),but it was not related to age(P=0.226),sex(P=0.352),clinical stage(P=0.986),lesion length(P=0.634)and lymphatic metastasis(P=0.581).AS for the general expression(P=0.504)and nuclear expression(P=0.080),there were no significant difference on the long-term survival rate beween the strong positive group and the positive and weakly positive group,but there was a decreased tendency about the nuclear expression of?-catenin.4.The general expression level of NRAGE protein in esophageal squamous cell carcinoma was positively correlated with the general expression level of?-catenin protein(?~2=11.675,P=0.001).The nuclear expression level of NRAGE protein in esophageal squamous cell carcinoma was positively correlated with the nuclear expression level of?-catenin protein(?~2=4.106,P=0.043).5.Cox regression multivariate analysis:As for NRAGE nuclear expression,the Risk of death in the strong positive group was9.22 times in the positive group and weakly positive group.However,there was no significant correlation between the expression level,gender,age,lesion length,clinical stages and the nuclear expression level of?-catenin in the long-term survival of patients.Conclusions:1.The nuclear and general expression of NRAGE protein in esophageal cancer tissue was negatively correlated with the short-term effect after radiotherapy,The nuclear expression of NRAGE was negatively correlated with the long-term survival rate.NRAGE may be an important index to reflect the radiation resistance of esophageal cancer and predict the short-term effect and the long-term survival after radiotherapy for esophageal carcinoma.2.The nuclear expression of?-catenin protein in esophageal cancer tissue was negatively correlated with the short-term effect after radiotherapy,the nuclear expression level of?-catenin in cancer cells may provide a reference for the prediction of short-term efficacy of esophageal squamous carcinoma.3.The nuclear and general expression level of NRAGE protein in esophageal squamous cell carcinoma was positively correlated with the nuclear and general expression level of?-catenin protein.NRAGE may participate in the formation of radioresistance by activating Wnt/?-catenin signaling pathway.