结直肠癌KRAS、NRAS、BRAF基因突变和MSI状态与其临床病理特征的关系

Association of KRAS,NRAS,BRAF gene mutations and MSI status with clinicopathological features in colorectal cancer

目的探讨结直肠癌中KRAS、NRAS、鼠类肉瘤滤过性毒菌致癌同源体B1(BRAF)基因突变和微卫星不稳定(MSI)状态与临床病理特征的关系。方法回顾性分析561例结直肠癌患者的临床病理资料;其中,行MSI状态检测的患者435例。采用突变扩增系统PCR法检测患者KRAS、NRAS和BRAF基因突变情况。依据MSI状态,将患者分为微卫星高度不稳定性(MSI-H)组(31例)、微卫星低度不稳定性(MSI-L)+微卫星稳定性(MSS)组(404例)。分析基因突变和MSI状态与患者临床病理特征的关系,以及基因突变与MSI状态的相关性。结果561例患者中,KRAS、NRAS、BRAF基因突变检出率分别为44.56%、1.96%、3.57%。KRAS基因突变与原发部位有关(P<0.05),NRAS基因突变与各临床病理特征均无关(P>0.05),BRAF基因突变与原发部位和分化程度有关(P<0.05)。435例患者中,MSI-H、MSI-L、MSS检出率分别为7.13%、2.76%、90.11%。MSI-H组与MSI-L+MSS组间原发部位、分化程度、肿块大小有统计学差异(P<0.05)。与MSI-L+MSS组相比,MSI-H组同时发生KRAS基因突变率更低,而BRAF基因突变率更高(P<0.05)。结论对结直肠癌患者进行KRAS、NRAS、BRAF基因突变和MSI状态联合检测,能更精准、有效地指导患者个体化治疗。

Objective To investigate the relationship of KRAS,NRAS,murine sarcoma infiltrating toxin B1(BRAF)gene mutation and microsatellite instability(MSI)status with clinicopathological features in colorectal cancer.Methods The clinicopathological data of 561 patients with colorectal cancer were retrospectively analyzed,of whom 435 patients underwent MSI status detection.The mutations of KRAS,NRAS and BRAF gene were detected by mutation amplification system PCR method.According to MSI status,435 patients were divided into two groups of A(MSI-H,31 cases)and B(MSI-L+MSS,404 cases).The relationship of gene mutation and MSI status with clinicopathological characteristics of the patients,and the correlation between gene mutation and MSI status were analyzed.Results Among 561 patients,the detection rates of KRAS,NRAS,and BRAF gene mutations were 44.56%,1.96%,and 3.57%,respectively.KRAS gene mutation was associated with primary site(P<0.05).NRAS gene mutation was not associated with clinicopathological features(P>0.05).BRAF gene mutation was associated with primary site and differentiation degree(P<0.05).Among 435 patients,the detection rates of MSI-H,MSI-L,and MSS were 7.13%,2.76%,and 90.11%,respectively.There were significant differences in the primary site,differentiation degree and tumor size between groups of A and B(P<0.05).Compared with group B,the rate of simultaneous KRAS gene mutation was lower,while the BRAF gene mutation rate was higher in group A(P<0.05).Conclusion Combined detection of KRAS,NRAS,BRAF gene mutations and MSI status in colorectal cancer patients can more accurately and effectively guide the individualized treatment.