结直肠癌KRAS、NRAS和BRAF基因突变及其与临床病理相关性研究  

Relationship between KRAS/NRAS/BRAF gene mutations and clinical pathological characteristics in colorectal cancer

作　　者：孙屏[1] 万佳艺[1] 吴靓骅 肖燕[1] 吕慧[1] 张熔熔[1] 

机构地区：[1]南京医科大学附属无锡市第二人民医院病理科,214002

出　　处：《中华普通外科杂志》2016年第1期50-54,共5页Chinese Journal of General Surgery

摘　　要：目的探讨结直肠癌患者KRAS、NRAS和BRAF基因突变与临床病理特征及预后的关系。方法应用实时荧光TaqMan探针法检测260例结直肠癌患者KRAS、NRAS和BRAF基因突变情况并应用统计学方法分析不同年龄、性别、肿瘤大小、分化程度等不同组别的基因突变情况与临床病理特征及预后的关系。结果（1）在260例结直肠癌患者中4例资料不详，有112例（43．1％）存在KRAS基因突变。KRAS基因突变率女性（50．O％，56／112）高于男性（37．8％，56／148），两者差异有统计学意义（P=0．05）。年龄i〉60岁患者中KRAS突变率（50．7％，70／138）高于年龄〈60岁患者的突变率（34．4％，42／122），两者差异有统计学意义（P=0．008）。KRAS突变型转移率和死亡率均高于野生型（P=0．004、P=0．037）。（2）检测结直肠癌中NRAS12、13、61密码子基因突变率为4．6％（12／260），年龄≥60岁患者中NRAS突变率（7．2％，10／138）高于年龄〈60岁患者的突变率（1．6％，2／122），分化好的结直肠癌患者的突变率（6．1％，12／196）高于分化差者的突变率（0／64），两者差异均有统计学意义（P=0．032、P=0．042）。（3）结直肠癌中BRAFV600E基因突变率为4．6％（12／260）。年龄≥60岁患者中BRAF突变率（7．2％，10／138）高于年龄〈60岁患者的突变率（1．6％，2／122）；有远处转移患者的突变率（10．7％，6／56）高于无远处转移者（3．0％，6／200）；肿瘤长径〉5cm的患者中的突变率（9．3％，8／86）高于长径〉3～≤5cm的患者（3．1％，4／128）及长径≤3cm患者（0／42）；差异均有统计学意义（P=0．032、P：0．026、P=0．038）。BRAF突变型转移率、复发率及死亡率均高于野生型（P=0．030、P=0．002、P=0．007）。结论结直肠癌患者中KRAS基因突变与性别和年龄相关，与术后的转移率及死亡率有关。NRAS基因突变与Objective To investigate the relationship between KRAS, NRAS and BRAF gene mutations and clinicopathological parameters in patients with colorectal carcinoma （CRC）. Methods By using TagMan real-time PCR method KRAS/NRAS/BRAF hotspot mutations were detected in 260 cases of CRC. The associations between KRAS/NRAS/BRAF mutation status and clinical pathological characteristics were analysed in different groups divided by gender, age, tumor size, tumor differentiation. Results （ 1 ） The KRAS hotspot mutations were G12D,G12A,G12R,GI2C,G12V,G12S in codon 12 and G13C,G13D in codon 13. They were identified in 43.1% CRC. KRAS mutation rate was higher in females than in males （P = 0. 05 ） and the mutation rate in patients i〉60 years was significantly higher than that in patients 〈 60 years（P = 0. 008 ）. The incidence of metastasis and mortality were higher in KRAS mutant than in KRAS wild type（P =0. 004,P =0. 037）. （2）The NRAS hotspot mutations were in codonl2,13 and 61. They were identified in 4. 6% CRC. NRAS mutation rate was significantly higher in patients ≥ 60 years and well- differentiated tumors （P = 0. 032 ,P = 0. 042）. （3） The mutation rate of BRAF V6OOE in CRC patients was 4. 6%. BRAF V600E mutation rate was significantly higher in patients ≥60 years, with distant metastases and tumors 〉 5 cm （ P = 0. 032, P = 0. 026, P =0. 038 ）. The incidence of metastasis and rucurrence andmortality were higher in BRAF mutant （ P = 0. 030, P = 0. 002, P =0. 007 ）. Conclusions In CRC patients, KRAS mutations correlate with demographic factors, metastasis and mortality, NRAS mutations correlate with age and tumor differentiation, while BRAF mutation correlate with age, tumor size, metastasis, recurrence and mortality.

关 键 词：结直肠肿瘤 癌基因 突变 病理学 临床 

分 类 号：R739.5[医药卫生—肿瘤]