三阴性乳腺癌患者MutT同源蛋白1基因状态与免疫治疗疗效及预后分析

Analysis of MutT homologous protein 1 gene status and immunotherapy efficacy and prognosis in patients with triple negative breast cancer

目的探讨三阴性乳腺癌(TNBC)患者MutT同源蛋白1(MTH1)基因状态与免疫治疗疗效及预后的关系。方法选择2017年1月至2019年10月于遂宁市中心医院进行免疫治疗的128例TNBC患者作为研究对象,根据MTH1基因状态分为MTH1突变组(46例)和Non-MTH1突变组(82例)。比较两组患者的临床资料、免疫治疗疗效及预后情况;Kaplan-Meier法绘制生存曲线分析MTH1基因状态与TNBC患者及采用不同方案治疗TNBC患者预后的关系;采用单因素及多因素Cox比例风险回归分析影响TNBC患者预后的因素,构建列线图预测模型并评价其预测效能。结果MTH1突变组与Non-MTH1突变组患者的肿瘤长径、病理类型、临床分期、脉管或神经浸润、淋巴结转移、治疗方案差异具有统计学意义(P<0.05);MTH1突变组患者治疗后的客观缓解率和疾病控制率均明显高于Non-MTH1突变组(P<0.05);采用免疫检查点抑制剂(ICIs)+抗血管生成方案治疗的患者中,MTH1突变组患者的3年无进展生存率及总生存率均明显高于Non-MTH1突变组(P<0.05);多因素Cox比例风险回归分析结果显示,年龄、肿瘤长径、组织学分级、临床分期、脉管或神经浸润、MTH1基因突变是影响患者3年无进展生存期(PFS)和总生存期(OS)的因素,月经状态也是影响患者3年PFS的因素(P<0.05);列线图模型预测TNBC患者3年无进展生存率和总生存率的区分度较高,准确性和有效性较好。结论MTH1基因状态与TNBC患者的临床特征及免疫治疗疗效有关,采用ICIs+抗血管生成方案治疗可提高MTH1基因突变患者的预后水平。

Objective To investigate the relationship between MutT homologous protein 1(MTH1)gene status and immunotherapy efficacy and prognosis in triple negative breast cancer(TNBC)patients.Methods 128 patients with TNBC who received immunotherapy in Suining Central Hospital from January 2017 to October 2019 were divided into MTH1 mutation group(n=46)and Non-MTH1 mutation group(n=82)according to MTH1 gene status.The clinical data,immunotherapy efficacy and prognosis of the two groups were compared.Kaplan-Meier survival curve was used to analyze the relationship between MTH1 gene status and the prognosis of TNBC patients and TNBC patients treated with different regimens.Univariate and multivariate Cox proportional hazard regression analysis was used to analyze the factors affecting the prognosis of TNBC patients.Results There were significant differences in tumor length,pathological type,clinical stage,vascular or nerve invasion,lymph node metastasis and treatment between MTH1 mutation group and Non-MTH1 mutation group(P<0.05).The objective remission rate and disease control rate of MTH1 mutation group were significantly higher than those of Non-MTH1 mutation group after treatment(P<0.05).In the patients treated with immune checkpoint inhibitors(ICIs)plus anti-angiogenesis regimen,the 3-year progression-free survival rate and overall survival rate in the MTH1 mutation group were significantly higher than those in the Non-MTH1 mutation group(P<0.05).Multivariate Cox proportional hazard regression analysis showed that age,tumor diameter,histological grade,clinical stage,vascular or nerve invasion and MTH1 gene mutation were factors affecting 3-year progression-free survival(PFS)and overall survival(OS).Menstrual status was also a factor affecting 3-year PFS(P<0.05).The nomogram model predicts high differentiation between 3-year PFS and overall survival in patients with TNBC.Conclusion The status of MTH1 gene is related to the clinical characteristics of patients with TNBC and the efficacy of immunotherapy.Treatment with ICIs+antiangiogenesis regimen can improve the prognosis of patients with MTH1 gene mutation.