晚期结直肠癌患者血浆循环肿瘤DNA与组织中KRAS及NRAS等基因突变一致性的影响因素分析

Analysis of influencing factors of KRAS/NRAS/BRAF/PIK3CA gene mutation consistency in patients with advanced colorectal cancer

目的分析血浆循环肿瘤DNA(ctDNA)与肿瘤组织DNA检测晚期结直肠癌患者KRAS/NRAS/BRAF/PIK3CA基因突变的一致性,同时探索影响两者一致性的因素。方法纳入2018年12月至2020年5月就诊于复旦大学附属中山医院的晚期结直肠癌患者165例,收集患者的ctDNA及组织基因检测结果、临床病理信息、治疗情况等。分析ctDNA与肿瘤检测KRAS/NRAS/BRAF/PIK3CA基因突变的一致性及影响因素。结果165例晚期结直肠癌患者[中位年龄61(28~84)岁,男102例,女63例]均接受了血浆ctDNA检测,ctDNA中KRAS、NRAS、BRAF、PIK3CA基因突变检出率分别为27.30%、2.42%、6.06%及9.70%。其中128例患者接受过组织基因检测,组织中KRAS、NRAS、BRAF、PIK3CA的突变检出率分别为30.47%、2.34%、7.03%及3.13%。血浆ctDNA与组织DNA检测KRAS/NRAS/RAF/PIK3CA基因突变的总体一致率为62.50%(Kappa=0.200,P=0.023)。单因素分析发现,初诊未治组以及肝转移组中基因检测的一致性较高[OR 95%CI为0.206(0.043~0.985),P=0.048],而肺转移组中的一致性较低。结论血浆ctDNA与组织DNA检测KRAS/NRAS/BRAF/PIK3CA基因突变存在一定的差异,抗肿瘤治疗以及肿瘤转移部位可能是影响不一致的重要因素。

Objective To analyze the consistency of plasma circulating tumor DNA(ctDNA)and tumor tissue DNA in detecting KRAS/NRAS/BRAF/PIK3CA gene mutations in patients with advanced colorectal cancer,and to explore the factors affecting the consistency.Methods Patients with advanced colorectal cancer who were treated in Zhongshan Hospital Fudan University from December 2018 to May 2020 were enrolled.The results of plasma and tissue gene detection,clinicopathological information and treatment were collected.The consistency and influencing factors of plasma and tissue KRAS/NRAS/BRAF/PIK3CA status were analyzed.Results The patients enrolled in this study all received plasma gene detection.The mutation rates of KRAS,NRAS,BRAF and PIK3CA in plasma were 27.30%,2.42%,6.06%and 9.70%,respectively.Among them,128 patients underwent tissue gene testing,and the mutation rates of KRAS,NRAS,BRAF and PIK3CA were 30.47%,2.34%,7.03%and 3.13%,respectively.The overall coincidence rate of KRAS/NRAS/BRAF/PIK3CA status by plasma and tissue was 62.50%(Kappa=0.200,P=0.023).Univariate analysis showed that the consistency of gene detection was higher in newly diagnosed untreated group and liver metastasis group,but lower in lung metastasis group.Conclusion Our real-world study found that there are some differences in KRAS/NRAS/BRAF/PIK3CA status between plasma and tissue.Anti-tumor therapy and metastatic sites may be important factors affecting the inconsistency.