胃癌组织中E-cadherin、Vimentin和错配修复相关蛋白的表达及与患者预后的关系

The expression of E-cadherin,Vimentin,and mismatch repair related proteins in gastric cancer tissue and their relationship with patient prognosis

目的:通过观察胃癌(gastric cancer,GC)患者E-cadherin、Vimentin和错配修复(mismatch repair,MMR)相关蛋白的表达,分析其影响GC患者预后的临床意义,探讨其与GC患者临床病理特征的关系。方法:选取2020年05月至2020年12月在承德市中心医院行GC手术并资料完整的患者104例,采用免疫组化染色检测E-cadherin、Vimentin、MMR相关蛋白表达,并分为E-cadherin、Vimentin阴性和阳性组,dMMR和pMMR组;采用Cox比例风险模型预测三者对GC患者总生存时间的影响,分为高低风险组,并用Kaplan-Meier进行生存分析。结果:104例患者中dMMR的概率为22.12%,E-cadherin阳性率为28.85%,Vimentin阳性率为51.92%。其中,dMMR和pMMR组相比,Lauren分型、pT和pTNM分期、肿瘤分化差异均有统计学意义(P<0.05);Lauren分型、pT和pTNM分期、肿瘤分化、脉管癌栓在Vimentin阳性和阴性组相比,差异均有显著意义(P<0.05);而E-cadherin阳性和阴性组仅在pTNM分期间相比有统计学差异(P<0.05)。随访结束后,GC患者的中位生存时间为19(15,24)个月,总生存率为76.9%;dMMR、E-cadherin阳性和Vimentin阳性生存率分别为83.6%、76.5%和63.0%(P<0.001)。根据预后模型的cutoff值(1.447)分为高风险和低风险,高风险GC患者发生死亡是低风险GC患者的8.20倍(2.75,24.40),前者中位生存时间(20个月)明显劣于后者(30个月),差异有统计学意义(P<0.001)。预后模型热图可知,dMMR的患者预后相对好,生存优势是pMMR患者的1.420倍,而Vimentin阳性的患者预后相对差,发生死亡的风险是阴性患者的2.433倍(P<0.001)。通过校准曲线和ROC分析,模型的预测和实测率比较接近(P=0.341>0.05),ROC下面积为0.88(0.78~0.97),敏感度和特异度分别为83.3%和57.5%(P<0.001);说明模型的区分度和校准度在接受范围内。结论:具有dMMR的患者预后更好,而Vimentin阳性表达的患者预后较差。基于MMR、E-cadherin、Vimentin蛋白的表达,预后模型的建立对GC患者疗后监测有一定的临床意义。

Objective:To analyze and explore the clinical significance and relationship of E-cadherin,Vimentin and mismatch repair proteins(MMR)and clinical pathological characteristics in patients with GC,using the expression of E-cadherin,Vimentin and MMR proteins observed.Methods:104 patients with complete data who underwent GC operation in Central Hospital of Chengde from May,2020 to December,2020 were enrolled.Immunohistochemical staining was used to observe E-cadherin,Vimentin and MMR proteins,which were divided into positive and negative groups of E-cadherin and Vimentin,as well as dMMR and pMMR groups.Cox proportional risk model was applied to predict the significance of E-cadherin,Vimentin and MMR proteins on overall survival(OS),which divided into high and low risk groups.Kaplan-Meier was performed to analyze the OS of patients with GC.Results:Among 104 cases,the rate of dMMR was 22.12%,the positive expression rates of E-cadherin and Vimentin were 28.85%and 51.92%,respectively.Among them,there were statistically significant differences in Lauren type,pT and pTNM stages,tumor differentiation between dMMR and pMMR groups(P<0.05).Lauren type,pT and pTNM stages,tumor differentiation,lymphovascular invasion were showed significant differences among positive and negative groups of Vimentin in statistics(P<0.05).Only pTNM stage was different between E-cadherin-positive group and E-cadherin-negative group(P<0.05).After follow-up,the median OS time was 19(15,24)months and the rate of OS was 76.9%.The rates of OS in dMMR,E-cadherin-positive and Vimentin-positive were 83.6%,76.5%and 63.0%,respectively(P<0.001).The death risk of the patients with high risk was 8.20 times(2.75,24.40)more than those with low risk based on the cutoff value(1.447)of prognostic model,the median survival time of the former(20 months)was obviously worse than that of the latter(30 months),with difference in statistics(P<0.001).Prognostic model heat map showed that the patients with dMMR had a good prognosis,and the survival advantage was 1.420 times more than that of the patients with pMMR.While there was a worse prognosis in Vimentin-positive patients,with 2.433 times in risk of death worse than that of patients with Vimentin-negative(P<0.001).The predicted and measured rates of the model were relatively close(P=0.341>0.05),the AUC value of ROC was 0.88(0.78~0.97),and the sensitivity and specificity were 83.3%and 57.5%,respectively(P<0.001),according to calibration curve and ROC analysis,indicating that the model's differentiation and calibration were within the acceptable range.Conclusion:Patients with dMMR have better prognosis,while those with positive of Vimentin have worse prognosis.Based on the expression of MMR,E-cadherin,Vimentin,the establishment of prognostic model has certain clinical significance for the patients with GC.