KRAS基因突变对阑尾腺癌的诊断价值  

The diagnostic value of KRAS gene mutation in appendiceal adenocarcinoma

作　　者：严礼平 毛卫波[1] 华芬芬 李恢曦 曹淑艳 Yan Liping;Mao Weibo;Hua Fenfen;Li Huixi;Cao Shuyan(Department of Pathology,Lishui Central Hospital,Lishui 323000,China;Department of Pathology,Zhejiang Putuo Hospital,Zhoushan 316100,China;Department of Pathology,Linfen People′s Hospital,Linfen 041000,China)

机构地区：[1]丽水市中心医院病理科,丽水323000 [2]浙江普陀医院病理科,舟山316100 [3]临汾市人民医院病理科,临汾041000

出　　处：《中国医师杂志》2023年第6期875-879,885,共6页Journal of Chinese Physician

基　　金：浙江省医药卫生科技计划项目(2022KY1426)。

摘　　要：目的分析阑尾腺癌患者Kirsten大鼠肉瘤病毒癌基因同源(KRAS)基因突变特点及其与Ras-Raf-丝裂原活化蛋白激酶/细胞外调节蛋白激酶(MAPK/ERK)信号通路活性的关系。方法选取丽水市中心医院2014年1月至2020年1月收治、经手术切除的41例阑尾腺癌患者为观察组,随机抽取50例同期手术的阑尾炎患者为对照组。统计其临床与随访资料,并采用Snapshot法测定患者组织KRAS基因的突变情况,采用蛋白免疫印迹(WB)试验测定癌组织MAPK/ERK信号通路关键蛋白的表达。比较KRAS突变与非KRAS突变阑尾腺癌患者临床特征和预后。结果观察组的KRAS基因突变率高于对照组(41.5%vs 10.0%),p-ARAF/ARAF、p-MEK1/MEK1、p-ERK1/ERK1蛋白表达水平也高于对照组,组间差异有统计学意义(均P<0.05)。观察组KRAS突变患者的p-ARAF/ARAF、p-MEK1/MEK1、p-ERK1/ERK1蛋白表达水平明显高于非KRAS突变者,KRAS突变患者Ⅳ期比例、癌胚抗原(CEA)、糖类抗原(CA)199及CA125的阳性率高于非KRAS突变患者,总生存期和无进展生存期短于非KRAS突变患者,差异有统计学意义(均P<0.05)。结论阑尾腺癌KRAS突变率较高,KRAS突变导致的MAPK/ERK信号通路激活可能在阑尾腺癌致病机制中发挥作用,具有深入研究的价值。Objective To analyze the mutation characteristics of Kirsten rat sarcoma virus oncogene homology(KRAS)gene in patients with appendiceal adenocarcinoma and its relationship with the activity of Ras Raf Mitogen activated protein kinase/extracellular regulated protein kinase(MAPK/ERK)signaling pathway.Methods A total of 41 patients with appendiceal adenocarcinoma who were treated in the Lishui Central Hospital from January 2014 to January 2020 were selected as the observation group,and 50 patients with Appendicitis who were operated at the same time were randomly selected as the control group.Clinical and follow-up data were collected,and the mutation of the KRAS gene in the patient′s tissue was measured using the snapshot method.The expression of key proteins in the MAPK/ERK signaling pathway in cancer tissue was measured using Western blotting(WB)assay.We compared the clinical characteristics and prognosis of patients with KRAS mutation and non KRAS mutation appendiceal adenocarcinoma.Results The KRAS gene mutation rate in the observation group was higher than that in the control group(41.5%vs 10.0%),and the expression levels of p-ARAF/ARAF,p-MEK1/MEK1,and p-ERK1/ERK1 proteins were also higher than those in the control group.The differences between the groups were statistically significant(all P<0.05).The protein expression levels of p-ARAF/ARAF,p-MEK1/MEK1,p-ERK1/ERK1 in KRAS mutation patients in the observation group were significantly higher than those in non KRAS mutation patients.The proportion of stage IV,positive rates of carcinoembryonic antigen(CEA),carbohydrate antigen(CA)199 and CA125 in KRAS mutation patients were higher than those in non KRAS mutation patients,and the survival time and progression free survival time were shorter than those in non KRAS mutation patients,with statistical significance(all P<0.05).Conclusions The mutation rate of KRAS in appendix adenocarcinoma is high,and the activation of MAPK/ERK signaling pathway caused by KRAS mutation may play a role in the pathogenesis of appendi

关 键 词：阑尾肿瘤 腺癌 突变 KRAS 丝裂原活化蛋白激酶 细胞外调节蛋白激酶 

分 类 号：R735.36[医药卫生—肿瘤]