二代测序技术检测284例结直肠癌突变基因特征分析

Analysis of mutant gene characteristics in 284 cases of colorectal cancer detected by next-generation sequencing technology

目的:探讨结直肠癌患者基因突变与临床病理特征关系及对生存期的影响。方法:二代测序技术检测基因突变状态,统计学方法分析基因突变与临床病理特征关系及对生存期的影响。结果:结直肠癌患者基因突变率为84.51%,其中KRAS以G12D、G12V和G13D突变为主,TP53常见突变为R273H和R248W,PIK3CA以E545K、E542K和H1047R突变为主,APC常见突变为T1556Nfs^(*)3和R1450^(*),BRAF突变类型为V600E、K601E和G469A。基因共突变率为64.79%,KRAS与TP53共突变最常见。男性及淋巴结转移者更易发生KRAS突变,肿瘤中-高期分化者易发生TP53突变,右半结肠、肿瘤溃疡型及中-高期分化者易发生PIK3CA突变。左半结肠易发生APC突变,而右半结肠易发生BRAF突变。KRAS和BRAF野生型比突变型患者可获得更长的生存期。结论:结直肠癌中突变频率较高的驱动基因分别为KRAS、TP53、PIK3CA、APC和BRAF,在不同临床病理特征中它们的突变率存在差异性,KRAS和BRAF突变型对患者生存期具有一定影响。

Objective:To explore the relationship between colorectal cancer patients gene mutation and clinicopathological characteristics,and the effect on survival.Methods:The gene mutation status was detected using next-generation sequencing technology,and the relationship between gene mutation and clinicopathological characteristics as well as the influence on survival was analyzed statistically.Results:The gene mutation rate in colorectal cancer patients was 84.51%,KRAS was dominated with G12D,G12V and G13D mutations,TP53 was dominated with R273H and R248W mutations,and PIK3CA was dominated with E545K,E542K and H1047R mutations.The frequent mutations were T1556Nfs~*3 and R1450~* in APC,BRAF was dominated with V600E,K601E and G469A.The gene co-mutation rate was 64.79%,and KRAS paired with TP53 was the commonest.Male and lymphatic metastases were more likely to occur KRAS mutation.TP53 mutation tend to occur in patients with medium-high tumor differentiation.PIK3CA mutations were more likely to occur in the right half colon,ulcerative tumors and medium-high stage differentiation.The left half colon was prone to APC mutation,and the right half colon was prone to BRAF mutation.KRAS and BRAF wild-type patients have a longer survival than mutant ones.Conclusion:The driver genes with high mutation frequency in colorectal cancer were KRAS,TP53,PIK3CA,APC and BRAF,and their mutation rates differ by clinicopathological features.KRAS and BRAF mutation had a certain impact on patient survival.