结直肠癌患者KRAS、NRAS、BRAF、HER2基因突变及MSI状态与临床特征的相关性分析  

Analysis of the relationship between KRAS,NRAS,BRAF,HER2 gene mutations and MSI status and clinical features in colorectal cancer patients

作　　者：赵洁 江珊 廖鑫 王晓凤 陈雪萍 吴江 李小松[1] 沈依帆 ZHAO Jie;JIANG Shan;LIAO Xin;WANG Xiaofeng;CHEN Xueping;WU Jiang;LI Xiaosong;SHEN Yifan(Clinical Molecular Medical Detection Center,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400042,China)

机构地区：[1]重庆医科大学附属第一医院临床分子医学检测中心,重庆400042

出　　处：《国际检验医学杂志》2024年第19期2360-2365,2371,共7页International Journal of Laboratory Medicine

基　　金：重庆英才·创新创业示范团队项目(CQYC202203091342)。

摘　　要：目的探讨结直肠癌患者的Kirsten大鼠肉瘤病毒癌基因同源物(KRAS)、神经母细胞瘤病毒癌基因RAS同源物(NRAS)、鼠类肉瘤滤过性毒菌致癌同源体B(BRAF)、人表皮生长因子受体2(HER2)基因突变及微卫星不稳定性(MSI)状态与临床病理特征之间的关系。方法收集2019年10月至2022年3月在该院接受治疗的226例结直肠癌患者的临床资料,采用二代测序技术检测KRAS、NRAS、BRAF、HER2基因突变情况和MSI状态,应用免疫组化法评估错配修复系统(MMR)状态,采用多因素Logistic回归分析KRAS、NRAS、BRAF、HER2与临床病理特征的关系。结果在226例结直肠癌患者中,KRAS基因突变频率为54.9%,NRAS基因突变频率为5.3%,BRAF基因突变频率为8.4%,HER2基因扩增突变频率为1.8%。黏液腺癌KRAS基因的突变频率高于普通腺癌(P<0.05),右半结肠癌KRAS基因突变的风险增加(OR=2.145,P=0.012)。而NRAS基因突变在左半结肠和直肠癌频率较高(P<0.05)。BRAF基因突变在低分化类型及微卫星高度不稳定(MSI-H)的结直肠癌中突变频率均较高(P<0.05),右半结肠BRAF基因突变的风险增加(OR=2.844,P=0.042)。HER2基因扩增突变表现肝肺等远处转移(P<0.05)。KRAS基因突变与NRAS、BRAF、HER2扩增突变是相互排斥的,差异有统计学意义(P<0.05)。MSI-H在右半结肠中的发生频率更高(P<0.05)。226例标本检出10例标本错配修复缺陷(dMMR)/MSI-H,8例标本dMMR/微卫生稳定,5例标本错配修复正常/MSI-H,dMMR和MSI-H之间存在中等程度的一致性(Kappa=0.575)。结论结直肠癌患者中,KRAS、NRAS、BRAF、HER2基因及MSI状态与临床病理特征有关,联合检测能够提供更准确、有效的数据,以指导患者的治疗临床用药和预后判断。Objective To investigate the relationship between Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma viral oncogene RAS homolog(NRAS),V-raf murine sarcoma viral oncogene homolog B(BRAF),human epidermal growth factor receptor 2(HER2)gene mutations and microsatellite instability(MSI)status and clinicopathological features in patients with colorectal cancer.Methods The clinical data of 226 patients with colorectal cancer treated in the hospital from October 2019 to March 2022 were collected.Next-generation sequencing technology was used to detect KRAS,NRAS,BRAF,HER2 gene mutations and MSI status.Immunohistochemistry was used to evaluate the mismatch repair system(MMR)status.Multivariate Logistic regression analysis was used to analyze the relationship between KRAS,NRAS,BRAF,HER2 gene mutations and clinicopathological features.Results Among 226 colorectal cancer patients,the mutation frequencies of KRAS,NRAS,BRAF and HER2 were 54.89%,5.3%,8.4%and 1.8%,respectively.The frequency of KRAS mutation in mucinous adenocarcinoma was higher than that in common adenocarcinoma(P<0.05).The risk of KRAS mutation in right colon cancer was increased(OR=2.145,P=0.012).NRAS gene mutation was more frequent in left colon and rectal cancer(P<0.05).The frequency of BRAF gene mutation was higher in poorly differentiated and microsatellite instability-high(MSI-H)colorectal cancer(P<0.05),and the risk of BRAF gene mutation in the right colon was increased(OR=2.844,P=0.042).HER2 gene amplification mutation showed distant metastasis(P<0.05).KRAS mutations were mutually exclusive with NRAS,BRAF and HER2 amplification mutations(P<0.05).MSI-H was more frequent in the right colon(P<0.05).Of the 226 cases,10 cases were defective mismatch repair(dMMR)/MSI-H,8 cases were dMMR/microsatellite stable,and 5 cases were proficient mismatch repair/MSI-H.There was a moderate agreement between dMMR and MSI-H(Kappa=0.575).Conclusion KRAS,NRAS,BRAF,HER2 and MSI status are associated with clinicopathological features in patients with colorectal canc

关 键 词：结直肠癌 基因突变 微卫星不稳定性 

分 类 号：R735.3[医药卫生—肿瘤]