首页|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

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

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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,KRASG12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);KRASG13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.
Comparison of clinicopathological characteristics,metastatic sites,and prognosis of Ⅰ~Ⅲ stage MSS type colorectal cancer patients with different RAS/BRAF codon mutation
Objective To investigate the correlation between different RAS/BRAF mutation sites and the clinicopathological characteristics,metastatic sites,and prognosis of patients with colorectal cancer.Methods A retrospective analysis was conducted on the clinicopathological data of 415 patients with stage Ⅰ-Ⅲ microsatellite stability(MSS)colorectal cancer who underwent radical surgery at the Department of Colorectal Surgery,The First Affiliated 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,BRAFv600E 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 stage Ⅰ-Ⅲ MSS 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 BRAFV600E mutation,and 47 cases(11.3%)of other RAS codon mutations.Clinicopathological characteristics analysis revealed that BRAFV600E 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 stage Ⅰ-Ⅲ colorectal cancer.Conclusions Different RAS/BRAF gene codon mutations are associated with distinct clinicopathological characteristics and organ metastatic sites in colorectal cancer.KRAS G13 codon mutation is an independent prognostic factor for poor prognosis in stage Ⅰ-Ⅲ colorectal cancer.It is recommended that routine detection of RAS/BRAF gene site mutations should be performed in stage Ⅰ-Ⅲ colorectal cancer patients to guide the follow-up management and help clinicians make rational clinical decisions after tumor recurrence.

colorectal cancerRAS/BRAF mutationclinicopathological featuresprognostic analysis

张翔、蒋微琴、华汉巨、刘硕、廖天一、蔡辉

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兰州大学第一临床医学院(兰州 730000)

甘肃省人民医院普外科(兰州 730099)

浙江大学医学院附属第一医院结直肠外科(杭州 310009)

甘肃省外科肿瘤分子诊断与精准治疗重点实验室(兰州 730000)

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结直肠癌 RAS/BRAF突变 临床病理特征 预后分析

国家自然科学基金甘肃省科技计划联合科研基金项目甘肃省人民医院优秀硕/博士生培育计划

8236049823JRRA153722GSSYD-20

2024

中国普外基础与临床杂志
四川大学华西医院

中国普外基础与临床杂志

CSTPCD
影响因子:0.858
ISSN:1007-9424
年,卷(期):2024.31(6)