错配修复蛋白状态与不良临床病理特征对结肠癌患者预后的交互作用分析  

Interaction analysis of mismatch repair protein and adverse clinicopathological features on prognosis of colon cancer

作　　者：李珂璇 赵富强 吴清彬 张峻岭[4] 罗双灵[5] 胡时栋[6] 吴斌 李鹤立 林国乐 邱辉忠 陆君阳 徐徕 王征[7] 杜晓辉[6] 康亮[5] 汪欣[4] 王自强 刘骞 肖毅 Li Kexuan;Zhao Fuqiang;Wu Qingbin;Zhang Junling;Luo Shuangling;Hu Shidong;Wu Bin;Li Heli;Lin Guole;Qiu Huizhong;Lu Junyang;Xu Lai;Wang Zheng;Du Xiaohui;Kang Liang;Wang Xin;Wang Ziqiang;Liu Qian;Xiao Yi(Division of Colorectal Surgery,Department of General Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China;Department of Colorectal Surgery,National Cancer Center,National Clinical Research Center for Cancer,Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Colorectal Cancer Center,West China School of Medicine,West China Hospital of Sichuan University,Chengdu 610041,China;Department of Gastrointestinal Surgery,Peking University First Hospital,Beijing 100034,China;Department of Colorectal Surgery,Institute of Gastroenterology of Guangdong Province,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases,The Sixth Afiliated Hospital,Sun Yat-sen University,Guangzhou 510655,China;Department of General Surgery,The First Medical Center,Chinese People's Liberation Army General Hospital,Beijing 100853,China;Department of Gastrointestinal Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院基本外科结直肠专业组,北京100730 [2]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院结直肠外科,北京100021 [3]四川大学华西临床医学院/华西医院结直肠肿瘤中心,成都610041 [4]北京大学第一医院胃肠外科,北京100034 [5]中山大学附属第六医院结直肠外科广东省胃肠病学研究所广东省结直肠盆底疾病研究重点实验室,广州510655 [6]解放军总医院第一医学中心普通外科,北京100853 [7]华中科技大学同济医学院附属协和医院胃肠外科,武汉430022

出　　处：《中华消化外科杂志》2024年第6期826-835,共10页Chinese Journal of Digestive Surgery

基　　金：中央高水平医院临床科研业务费资助(2022-PUMCH-C-027)。

摘　　要：目的探讨错配修复蛋白状态与不良临床病理特征对Ⅰ~Ⅲ期结肠癌患者预后的交互效应。方法采用回顾性队列研究方法。收集2016年1月至2017年12月全国7家医院收治的1650例Ⅰ~Ⅲ期结肠癌患者的临床病理资料;男963例,女687例;年龄为62(53,71)岁。1650例患者根据错配修复蛋白状态分为错配修复蛋白表达缺失(dMMR)230例与错配修复蛋白表达完整(pMMR)1420例。观察指标:(1)不同错配修复蛋白状态患者的临床病理特征比较。(2)影响dMMR患者生存结局的因素分析。(3)影响pMMR患者生存结局的因素分析。(4)错配修复蛋白状态与不良临床病理特征对生存结局影响的交互作用分析。正态分布的计量资料以x±s表示,组间比较采用独立样本t检验;偏态分布的计量资料以M(Q_(1),Q_(3))表示,组间比较采用Mann-WhitneyU检验。计数资料以绝对数表示,组间比较采用χ^(2)检验或Fisher确切概率法。等级资料采用Mann-WhitneyU检验。缺失值使用随机森林插补法进行数据插补。单因素分析采用COX比例风险回归模型。多因素分析采用COX逐步回归(向前逐步回归法)。乘法交互效应的系数使用COX比例风险回归模型的交互项系数获得。加法交互效应使用交互作用超额相对危险度(RERI)进行评价。结果(1)不同错配修复蛋白状态患者的临床病理特征比较。dMMR和pMMR患者年龄、T分期、淋巴结检出数目、淋巴结检出数目<12枚、高级别肿瘤比较,差异均有统计学意义(P<0.05)。(2)影响dMMR患者生存结局的因素分析。多因素分析结果显示:T分期、N分期、淋巴结检出数目<12枚是影响dMMR患者无病生存的独立因素(风险比=3.548,2.589,6.702,95%可信区间为1.460~8.620,1.064~6.301,1.886~23.813,P<0.05);年龄、N分期是影响dMMR患者总生存的独立因素(风险比=1.073,10.684,95%可信区间为1.021~1.126,2.311~49.404,P<0.05)。(3)影响pMMR患者生存结局的因素分析。多因素分Objective To investigate the interactive effect of mismatch repair(MMR)protein status and adverse clinicopathological features on prognosis of stageⅠ-Ⅲcolon cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 1650 patients with colon cancer of stageⅠ-Ⅲwho were admitted to 7 hospitals in China from January 2016 to December 2017 were collected.There were 963 males and 687 females,aged 62(53,71)years.Patients were classified as 230 cases of MMR deficiency(dMMR)and 1420 cases of MMR proficiency(pMMR)based on their MMR protein status.Observation indicators:(1)comparison of clinicopathological characteristics between patients of different MMR protein status;(2)analysis of factors affecting the survival outcomes of patients of dMMR;(3)analysis of factors affecting the survival outcomes of patients of pMMR;(4)interaction analysis of MMR and adverse clinicopathological features on survival outcomes.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was conducted using the independent t test.Measurement data with skewed distribution were represented as M(Q_(1),Q_(3)),and comparison between groups was conducted using the Mann-Whitney U test.Count data were described as absolute numbers,and comparison between groups was conducted using the chi-square test or Fisher exact probability.Comparison of ordinal data was conducted using the Mann-Whitney U test.The random forest interpolation method was used for missing values in data interpolation.Univariate analysis was conducted using the COX proportional risk regression model,and multivariate analysis was conducted using the COX stepwise regression with forward method.The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model.Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction(RERI).Results(1)Comparison of clinicopathological characteristics b

关 键 词：结肠肿瘤 不良病理特征 错配修复 生存 交互作用 

分 类 号：R735.35[医药卫生—肿瘤]