结直肠癌组织中KRAS和BRAF基因突变与临床病理特征及预后的关系  

Relationship between KRAS and BRAF gene mutations and clinicopathology and prognosis in colorectal cancer tissues

作　　者：陈海霞[1] 何亚楠 王维娜[1] 马晓梅[1] CHEN Haixia;HE Yanan;WANG Weina;MA Xiaomei(Pathology Department,Affiliated Tumor Hospital of Xinjiang Medical University,Xinjiang Urumqi 830011,China)

机构地区：[1]新疆医科大学附属肿瘤医院病理科,新疆乌鲁木齐830011

出　　处：《现代肿瘤医学》2021年第4期626-631,共6页Journal of Modern Oncology

基　　金：新疆维吾尔自治区自然科学基金(编号:2018D01C254)。

摘　　要：目的:探讨结直肠癌组织中KRAS和BRAF基因突变与临床病理和预后的关系。方法:采用扩增阻滞突变系统(ARMS)方法对134例结直肠癌组织进行回顾性分析。结果:134例CRC组织中KRAS基因突变率49.3%(66/134),第2外显子突变率42.5%(57/134),其中12及13密码子突变率分别为35.1%(47/134)和7.5%(10/134),第3外显子61密码子突变率1.5%(2/134),第4外显子117/146密码子突变率5.2%(7/134),BRAF V600E突变率4.5%(6/134)。左半结肠KRAS基因突变率54.5%(54/99)高于右半结肠34.3%(12/35),差异有统计学意义(P<0.05),右半结肠BRAF基因突变率14.3%(5/35)高于左半结肠1.0%(1/99),差异有统计学意义(P<0.05),而KRAS和BRAF基因突变与性别、年龄、民族、肿块大小、分化程度、淋巴结转移及病理分期等临床病理特征,差异均无统计学意义(P>0.05)。KRAS基因突变型CRC患者的中位生存时间48个月(39.9%),与野生型47个月(46.2%)相比较,差异无统计学意义(P>0.05)。BRAF基因突变型CRC患者的中位生存时间21个月(26.7%),与野生型48个月(44.7%)相比较,差异有统计学意义(P<0.05)。多因素COX回归风险模型结果显示,BRAF基因突变型是CRC患者预后不良的独立危险因素(B=1.664,OR=5.278,95%CI:1.505~18.516,P<0.05),而性别、年龄、民族、肿块大小、分化程度、肿瘤部位、淋巴结转移及病理分期均不是CRC患者生存时间的独立危险因素(P>0.05)。结论:CRC组织中KRAS基因突变率高,BRAF基因突变率低。KRAS和BRAF基因突变型与肿瘤部位有关。BRAF基因突变型是CRC预后不良的独立危险因素。Objective:To explore the relationship between KRAS and BRAF gene mutations and clinicopathology and prognosis in colorectal cancer(CRC).Methods:A retrospective analysis of 134 cases of colorectal cancer tissues were performed using the amplified block mutation system(ARMS)method.Results:The mutation rate of KRAS gene in 134 cases of CRC was 49.3%(66/134),and the exon 2 mutation rate was 42.5%(57/134),including the 12 and 13 codon mutation rates,which were 35.1%(47/134)and 7.5%(10/134).The exon 3 mutation rate of codon 61 was 1.5%(2/134).The exon 4 mutation rate of 117/146 codons were 5.2%(7/134).The BRAF V600E mutation rate was 4.5%(6/134).The KRAS mutation rate was 54.5%(54/99)in the left colon,higher than right colon 34.3%(12/35).The difference was statistically significant(P<0.05).The BRAF gene mutation rate was 14.3%(5/35)in the right colon,higher than left colon 1.0%(1/99).The difference was statistically significant(P<0.05).However,there were not statistically significant differences between KRAS and BRAF gene mutations and clinicopathological features such as gender,age,nation,tumor size,differentiation degree,lymphatic metastasis and pathological stage(P>0.05).The median survival time of CRC patients with KRAS gene mutation was 48 months (39.9%) and compared with 47 months (46.2%) of CRC patients with wild,the difference was not statistically significant( P >0.05).The median survival time of CRC patients with BRAF gene mutation was 21 months (26.7%),and compared with 48 months (44.7%) for CRC patients with wild type,the difference was statistically significant ( P <0.05).The results of multivariate COX regression risk model showed that BRAF gene mutation was an independent risk factor for poor prognosis in CRC patients(B=1.664,OR=5.278,95%CI:1.505~18.516, P <0.05),but gender,age,nation,tumor size,differentiation degree,tumor location,lymphatic metastasis and pathological stage were not independent risk factors for survival time of CRC patients ( P >0.05). Conlusion: The mutation rate of KRAS gene is high,

关 键 词：结直肠癌 KRAS BRAF 基因突变 临床病理 预后 

分 类 号：R735.35[医药卫生—肿瘤] R735.37[医药卫生—临床医学]