Ⅰ~Ⅲ期MSS型结直肠癌患者RAS/BRAF基因不同密码子突变的临床病理特征、转移部位及临床预后比较  

Comparison of clinicopathological characteristics,metastatic sites,and prognosis ofⅠ-Ⅲstage MSS type colorectal cancer patients with different RAS/BRAF codon mutation

作　　者：张翔 蒋微琴[3] 华汉巨[3] 刘硕 廖天一 蔡辉 ZHANG Xiang;JIANG Weiqin;HUA Hanju;LIU Shuo;LIAO Tianyi;CAI Huit(The First Clinical Medical College,Lanzhou University,Lanzhou 730000,P.R.China;General Surgery Department of Gansu Provincial People's Hospital,Lanzhou 730099,P.R.China;Department of Colorectal Surgery,The First Afiliated Hospital,Zhejiang University School of Medicine,Hangzhou 30009,P.R.China;Key Laboratory of Molecular Diagnosis and Precision Medicine for Surgical Oncology in Gansu Province,Lanzhou 730000,P.R.China)

机构地区：[1]兰州大学第一临床医学院,兰州730000 [2]甘肃省人民医院普外科,兰州730099 [3]浙江大学医学院附属第一医院结直肠外科,杭州310009 [4]甘肃省外科肿瘤分子诊断与精准治疗重点实验室,兰州730000

出　　处：《中国普外基础与临床杂志》2024年第6期682-689,共8页Chinese Journal of Bases and Clinics In General Surgery

基　　金：国家自然科学基金(项目编号:82360498);甘肃省科技计划联合科研基金项目(项目编号:23JRRA1537);甘肃省人民医院优秀硕/博士生培育计划(项目编号:22GSSYD-20)。

摘　　要：目的探讨不同RAS/BRAF突变位点与结直肠癌患者的临床病理特征关系、转移部位及预后的差异。方法回顾性收集2017年3月1日至2022年10月1日期间在浙江大学第一附属医院结直肠外科以及甘肃省人民医院普外科行根治术的415例Ⅰ~Ⅲ期微卫星稳定(microsatellite stability,MSS)型结直肠癌且有第二代测序数据患者的临床病理资料,根据RAS/BRAF有无突变及突变位点的不同分为5组:RAS/BRAF野生组、KRAS G12密码子突变组、KRAS G13密码子突变组、BRAFV600E突变组和其他RAS密码子突变组。分别比较4组RAS/BRAF突变结直肠癌患者与RAS/BRAF野生型结直肠癌患者的临床病理特征差异和临床预后差异。结果在Ⅰ~Ⅲ期MSS型结直肠癌患者中,RAS/BRAF未发生突变即野生型166例(40.0%),KRAS G12突变124例(29.9%),KRAS G13突变55例(13.3%),BRAFV600E突变23例(5.5%),其他RAS密码子突变47例(11.3%)。临床病理特征分析结果显示,BRAFV600E突变与黏液腺癌相关(P=0.033)。与野生组相比,KRAS G12突变可增加异时性肺转移发生的概率(P=0.003),降低异时性肝转移发生的概率(P=0.013);KRAS G13突变和其他RAS突变可增加异时性肺转移发生的概率(P=0.004,P=0.006)。单因素及多因素Cox比例风险回归分析结果显示,在RAS/BRAF密码子突变中,只有KRAS G13突变是Ⅰ~Ⅲ结直肠癌预后不良的独立预测因素。结论不同的RAS/BRAF基因密码子突变伴随着不同的结直肠癌临床病理特征和器官转移部位,KRAS G13密码子突变是Ⅰ~Ⅲ结直肠癌预后不良的独立预后因素。建议临床上对Ⅰ~Ⅲ期结直肠癌患者应常规检测RAS/BRAF基因位点突变情况,以指导结直肠癌患者的随访管理,帮助临床医生在肿瘤复发后做出合理的临床决策。Objective e To investigate the correlation between different RAS/BRAF mutation sites and the clinicopathological characteristics,metastatic sites,and prognosis of patients with colorectal cancer.MethodsA retrospective analysis was conducted on the clinicopathological data of 415 patients with stageⅠ-Ⅲmicrosatellite stability(MSS)colorectal cancer who underwent radical surgery at the Department of Colorectal Surgery,The First Affliated Hospital of Zhejiang University,and the Department of General Surgery,Gansu Provincial People's Hospital,from March 1,2017,to October 1,2022,and had next-generation sequencing data.According to the presence and sites of RAS/BRAF mutations,patients were divided into five groups:RAS/BRAF wild-type group,KRAS G12 codon mutation group,KRAS G13 codon mutation group,BRAFvo0 mutation group,and other RAS codon mutation group.The clinicopathological characteristics and prognostic differences between the four groups of RAS/BRAF mutant colorectal cancer patients and the RAS/BRAF wild-type colorectal cancer patients were compared.Results Among stageⅠ-ⅢMSS colorectal cancer patients,there were 166 cases(40.0%)of wild-type RAS/BRAF without mutation,124 cases(29.9%)of KRAS G12 mutation,55 cases(13.3%)of KRAS G13 mutation,23 cases(5.5%)of BRAFv60E mutation,and 47 cases(11.3%)of other RAS codon mutations.Clinicopathological characteristics analysis revealed that BRAFvoE mutation was associated with mucinous adenocarcinoma(P=0.033).Compared with the wild-type group,KRAS G12 mutation could increase the probability of metachronous lung metastasis(P=0.003)and reduce the probability of metachronous liver metastasis(P=0.013);the KRAS G13 mutation and other RAS mutations could increase the probability of metachronous lung metastasis(P=0.004,P=0.006).Univariate and multivariate Cox proportional hazards regression analysis showed that among the RAS/BRAF codon mutations,only KRAS G13 mutation was an independent prognostic factor for poor prognosis in stageⅠ-Ⅲcolorectal cancer.Conclusions Different

关 键 词：结直肠癌 RAS/BRAF突变 临床病理特征 预后分析 

分 类 号：R735.34[医药卫生—肿瘤]