错配修复功能缺陷的结直肠癌术后患者预后影响因素的分析  

Analysis of prognostic factors in colorectal cancer patients with mismatch repair deficiency after radical surgery

作　　者：黄庆 邹旻红[3] 蒋叶[4] 李旺林 曹杰 Huang Qing;Zou Minhong;Jiang Ye;Li Wanglin;Cao Jie(Department of General Surgery,Guangzhou First People’s Hospital,the Second Affiliated Hospital of South China Univer sity of Technology,Guangzhou 510180,China)

机构地区：[1]广州市第一人民医院(华南理工大学附属第二医院)综合外科,广州510180 [2]广州市第一人民医院(华南理工大学附属第二医院)消化疾病中心,广州510180 [3]中山大学附属第三医院超声科,广州510630 [4]中山大学附属第三医院病理科,广州510630

出　　处：《新医学》2021年第7期482-487,共6页Journal of New Medicine

基　　金：国家自然科学基金(81871943);广东省医学科研基金(A2019526);广州市科技计划项目(202102010024)。

摘　　要：目的探讨错配修复功能缺陷(dMMR)的结直肠癌术后患者错配修复(MMR)蛋白表达情况和预后影响因素,分析辅助化学治疗(化疗)对Ⅱ、Ⅲ期dMMR结直肠癌预后的影响。方法回顾性分析dMMR结直肠癌根治性手术病例106例,分析其MMR蛋白(包括MLH1、MSH2、MSH6、PMS2)缺失的情况。单因素和多因素Cox分析dMMR结直肠癌术后患者的无病生存期(DFS)和总生存期(OS)预后影响因素,Kaplan-Meier法分析Ⅱ、Ⅲ期dMMR结直肠癌化疗组与无化疗组的差异。结果MLH1/PMS2蛋白缺失率为45%,MSH2/MSH6蛋白缺失率为18%,单个MLH1蛋白的缺失率为11%,单个MSH6蛋白的缺失率为9%,单个PMS2蛋白的缺失率为12%。单因素Cox分析显示,术前癌胚抗原(CEA)≥5 ng/ml、直肠、T4、N1、N2、神经侵犯、脉管侵犯和淋巴结获取数量<12枚是dMMR结直肠癌患者DFS的危险因素;术前CEA≥5 ng/ml、术前糖链抗原199(CA199)≥34 U/ml、直肠、T4、N1、N2和淋巴结获取数量<12枚是dMMR结直肠癌患者OS的危险因素。多因素Cox分析显示术前CEA≥5 ng/ml[HR=2.68(1.08~6.63),P=0.034]、N1[HR=2.94(1.12~7.73),P=0.028]、N2[HR=9.31(2.49~34.77),P=0.001]和淋巴结获取数量<12枚[HR=3.97(1.66~9.50),P=0.002]是dMMR结直肠癌患者DFS的独立危险因素;N1[HR=6.64(2.25~19.64),P=0.001]、N2[HR=9.68(1.92~48.96,P=0.006)]和淋巴结获取数量<12枚[HR=6.36(2.28~17.73),P<0.001]是dMMR结直肠癌患者OS的独立危险因素。Ⅱ、Ⅲ期dMMR结直肠癌化疗组与无化疗组的DFS和OS比较差异无统计学意义(P均>0.05)。结论术前CEA≥5 ng/ml是dMMR结直肠癌患者DFS的独立危险因素;N1、N2和淋巴结获取数量<12枚是dMMR结直肠癌患者DFS和OS的独立危险因素。辅助化疗不影响Ⅱ、Ⅲ期dMMR结直肠癌的预后。Objective To investigate the MMR protein expression and the prognostic factors of patients with mismatch repair-deficient(dMMR)colorectal cancer(CRC)after radical surgery and to evaluate the effect of adjuvant chemotherapy on the clinical prognosis of stageⅡandⅢdMMR CRC patients.Methods A total of 106 patients with dMMR CRC undergoing radical surgery were enrolled and MMR proteins deficiency were analyzed.Prognostic factors for disease-free survival(DFS)and overall survival(OS)of patients with dMMR CRC after surgery were identified by univariate and multivariate Cox regression analyses.DFS and OS of stageⅡandⅢdMMR CRC patients were statistically compared between the chemotherapy and non-chemotherapy groups by Kaplan-Meier survival analysis.Results The MLH1/PMS2 protein deletion rate was 45%,the MSH2/MSH6 protein deletion rate was 18%,the single MLH1 protein deletion rate was 11%,the single MSH6 protein deletion rate was 9%,and the single PMS2 protein deletion rate was 12%.Univariate Cox regression analysis showed that preoperative CEA level harvested≥5 ng/ml,rectum,T4,N1,N2,nerve invasion,vascular invasion,and the number of lymph nodes harvested<12 were the risk factors for DFS in patients with dMMR CRC.Preoperative CEA level harvested≥5 ng/ml,preoperative CA199 level harvested≥34 U/ml,rectum,T4,N1,N2,and the number of lymph nodes harvested<12 were the risk factors for OS in dMMR CRC patients.Multivariate Cox regression analysis demonstrated that preoperative CEA level harvested≥5 ng/ml(HR=2.68(1.08~6.63),P=0.034),N1(HR=2.94(1.12~7.73),P=0.028),N2(HR=9.31(2.49~34.77),P=0.001),and the number of lymph node harvested<12(HR=3.97(1.66~9.50),P=0.002)were the independent risk factors for DFS in dMMR CRC patients.N1(HR=6.64(2.25~19.64),P=0.001),N2(HR=9.68(1.92~48.96),P=0.006),and the number of lymph nodes harvested<12(HR=6.36(2.28~17.73),P<0.001)were the independent risk factors for OS in dMMR CRC patients.DFS and OS of stageⅡandⅢdMMR CRC patients did not significantly differ between the chemotherapy

关 键 词：结直肠癌 错配修复功能缺陷 预后 根治性手术 

分 类 号：R735.34[医药卫生—肿瘤]