TOP2A与胃癌术后辅助化疗及表柔比星疗效的关系

Association of TOP2A with the efficacy of adjuvant chemotherapy and epirubicin in gastric cancer

目的探讨拓扑异构酶ⅡA(TOP2A)与胃癌术后辅助化疗及表柔比星疗效的关系。方法筛选D2根治术后接受了辅助化疗的胃腺癌患者,采用免疫组化染色检测其石蜡包埋的肿瘤组织中TOP2A蛋白的表达,分析TOP2A与患者无病生存期(DFS)及总生存期(OS)的关系,并亚组分析TOP2A与含表柔比星方案辅助化疗疗效的关系。结果 109例患者入选,其中接受含表柔比星方案辅助化疗的患者44例。TOP2A表达水平与胃癌各临床病理特征均无关(P>0.05)。KaplanMeier生存分析显示,TOP2A蛋白低表达患者的3年无病生存率和3年生存率均显著高于高表达者(79.8%vs.57.1%和88.0%vs.65.0%;P均<0.05)。在接受含表柔比星方案辅助化疗的胃癌患者中,TOP2A蛋白低表达者的3年无病生存率显著高于高表达者(83.3%vs.50.0%,P<0.05),而3年生存率的差异无统计学意义(91.7%vs.62.2%,P=0.068)。多因素Cox比例风险回归模型显示,组织学分级Ⅲ级(HR=3.02,95%CI:1.41~6.46;P=0.004)和TOP2A蛋白高表达(HR=3.51,95%CI:1.06~11.58;P=0.039)是影响胃癌OS的独立风险因素。结论 TOP2A可能与胃癌术后辅助化疗及表柔比星疗效有关,是疗效预测潜在的分子标志。

Objective To investigate the association of TOP2A with the efficacy of adjuvant chemotherapy and epirubicin in gastric cancer.Methods Patients with gastric adenocarcinoma who had received radical gastrectomy of D2 and adjuvant chemotherapy after surgery were selected.The expression of TOP2A protein in paraffin-embedded tumor tissues was detected by immunohistochemistry,and its correlations with disease-free survival（DFS） and overall survival（OS） of patients were analyzed.Results A total of 109 patients were enrolled including 44 epirubicin-treated patients.The expression level of TOP2A protein was not relative with clinicopathologic characteristics of gastric cancer（P 0.05）.Kaplan-Meier survival analyses showed that the 3-year disease-free survival rate and3-year overall survival rate in patients with low expression of TOP2A protein were higher than those with high expression（79.8% vs.57.1% and 88.0% vs.65.0%,respectively;both P 0.05）.In patients with gastric cancer treated with epirubicin adjuvant chemotherapy,such superiority associated with low expression of TOP2A protein was also observed for DFS（83.3% vs.50.0%;P 0.05）and OS had a trend to be significantly different（91.7% vs.62.2%;P = 0.068）.Furthermore,Multivariate Cox regression proportional hazard analysis showed that histological grade of Ⅲ（HR = 3.02,95% CI：1.41-6.46;P = 0.004） and TOP2A high expression（HR = 3.51,95% CI：1.06-11.58;P = 0.039） were the independent risk factor of OS in gastric cancer.Conclusion The TOP2A expression may be associated with the efficacy of adjuvant chemotherapy and epirubicin in gastric cancer,and it is a potential molecular marker for efficacy prediction.