PP2A与进展期胃癌患者预后关系的生存分析

Survival analysis of the relationship between PP2A and prognosis ofpatients with advanced gastric cancer

目的:探讨蛋白磷酸酯酶2A(PP2A)与进展期胃癌患者预后的关系。方法:选取2016年1月至2017年9月在邯郸市中心医院就诊的95例进展期胃癌患者作为研究对象,临床分期为Ⅱ~Ⅲ期,均接受根治性手术治疗。分析PP2A与进展期胃癌患者术后肿瘤复发转移和死亡的相关性,绘制PP2A预测进展期胃癌患者根治术后5年内肿瘤复发转移和死亡的受试者工作特征(ROC)曲线和决策曲线,以PP2A的两个最佳诊断截点将所有患者分为A、B组及C、D组,Kaplan-Meier生存分析比较两组患者根治术后5年无病生存率和总生存率。结果:多因素Cox回归分析结果显示,血管侵犯、侵犯深度以及PP2A为影响进展期胃癌患者根治术后5年内肿瘤复发转移和死亡的独立预测因素(P<0.05)。ROC曲线分析结果显示,血管侵犯、侵犯深度以及PP2A预测进展期胃癌患者根治术后5年内肿瘤复发转移的曲线下面积(AUC)分别为0.782(95%CI:0.712~0.834)、0.854(95%CI:0.791~0.913)以及0.754(95%CI:0.713~0.792),PP2A的最佳诊断截点为4.35 pg·ml-1,三者联合预测的AUC为0.963(95%CI:0.911~0.987);血管侵犯、侵犯深度以及PP2A预测进展期胃癌患者根治术后5年内死亡的AUC分别为0.756(95%CI:0.714~0.795)、0.869(95%CI:0.816~0.907)以及0.784(95%CI:0.732~0.839),PP2A的最佳诊断截点为4.41 pg·ml-1,三者联合预测的AUC为0.957(95%CI:0.921~0.984)。Kaplan-Meier生存分析结果显示,A组进展期胃癌患者根治术后1、3、5年无病生存率明显高于B组(71.4%、45.6%、32.5%vs. 52.3%、19.7%、17.2%,P<0.05),C组进展期胃癌患者根治术后1、3、5年总生存率明显高于D组(91.3%、83.7%、64.6%vs. 81.4%、54.5%、43.8%,P<0.05)。决策曲线分析结果显示,在大多数合理阈值概率范围内,血管侵犯、侵犯深度以及PP2A预测进展期胃癌患者根治术后5年内肿瘤复发转移和死亡均具有良好的净收益率。结论:血清PP2A表达水平较低的进展期胃癌患者,其根治术后肿瘤复发转移风险高,无病生存率和总生存率低。

Objective:To investigate the relationship between protein phosphatase 2A(PP2A)and the prognosis of patients with advanced gastric cancer.Methods:95 patients with advanced gastric cancer who were treated in our hospital from January 2016 to September 2017 were selected as the study objects.The clinical stages were Phase II to III,and all patients received radical surgery.The correlation between PP2A and tumor recurrence,metastasis and death of patients with advanced gastric cancer after radical surgery was analyzed,and the ROC curve and decision curve of PP2A predicting tumor recurrence,metastasis and death of patients with advanced gastric cancer within 5 years after radical surgery were drawn.All patients were divided into group A and group B,group C and group D according to the best diagnostic cut-off point of PP2A.Kaplan Meier survival analysis was used to compare the 5-year disease-free survival rate and overall survival rate of patients in the two groups after radical surgery.Results:Multivariate Cox regression analysis showed that vascular invasion,invasion depth and PP2A were independent predictors of tumor recurrence,metastasis and death in patients with advanced gastric cancer within 5 years after radical surgery(P<0.05).The ROC analysis results showed that the area under the curve(AUC)of vascular invasion,depth of invasion and PP2A predicting tumor recurrence and metastasis in patients with advanced gastric cancer within 5 years after radical surgery were 0.782(95%CI:0.712-0.834),0.854(95%CI:0.791-0.913)and 0.754(95%CI:0.713-0.792)respectively.The best diagnostic cutoff point of PP2A was 4.35 pg·mL-1.The AUC predicted by the three methods was 0.963(95%CI:0.911-0.987).The AUC of vascular invasion,depth of invasion,and PP2A predicting the death within 5 years after radical surgery in patients with advanced gastric cancer were 0.756(95%CI:0.714-0.795),0.869(95%CI:0.816-0.907),and 0.784(95%CI:0.732-0.839),respectively.The best cutoff point for diagnosis of PP2A was 4.41 pg·ml-1.The AUC predicted by the three methods was 0.957(95%CI:0.921-0.984).Kaplan-Meier survival analysis showed that the 1-year,3-year and 5-year disease-free survival rate of patients with advanced gastric cancer in group A was significantly higher than that in group B(71.4%,45.6%,32.5%vs.52.3%,19.7%,17.2%,P<0.05),and the 1-year,3-year and 5-year overall survival rate of the patients with advanced gastric cancer in group C was significantly higher than that in group D(91.3%,83.7%,64.6%vs.81.4%,54.5%,43.8%,P<0.05).The results of decision curve analysis showed that,within the most reasonable threshold probabilities,vascular invasion,invasion depth and PP2A predicted tumor recurrence,metastasis and death in patients with advanced gastric cancer within 5 years after radical surgery had good net gain.Conclusion:Patients with advanced gastric cancer with low serum PP2A expression level have a high risk of tumor recurrence and metastasis after radical surgery,and have a low disease-free survival rate and overall survival rate.