同时性结直肠癌原发灶和肝转移灶中KRAS基因突变的一致性分析

Consistency analysis of KRAS mutation between primary tumors and paired liver metastases in synchronous colorectal live metastasis

目的:比较KRAS基因突变率在结直肠癌原发灶和肝转移灶之间的差异,并探索KRAS突变对初始可切除同时性结直肠癌肝转移患者同期切除术后预后的影响。方法:回顾性分析同期切除的139例同时性结直肠癌肝转移患者的临床病理资料。运用Pyrosequencing焦磷酸测序法检测原发灶和转移灶中KRAS基因的突变情况,比较两者之间KRAS突变率的差异;同时采用Kaplan-Meier生存分析和Cox回归模型分析KRAS突变对预后的影响。结果:139例患者的围手术期死亡率为0%,并发症发生率为28.1%。28.8%(40/139)的患者原发灶中KRAS发生了突变;KRAS突变和临床病理因素无明显相关性。KRAS突变率在原发灶中为29.5%(28/95),在转移灶中为31.6%(30/95),两者间差异无显著统计学意义(P=0.157)。KRAS突变与总生存时间无相关性,与较短的无疾病生存时间相关(P=0.041),且是短的无疾病生存时间的独立预后因素(P=0.012)。结论:KRAS突变率在原发灶和转移灶中存在高度一致性,且与短的无疾病生存时间相关,在决定同期手术决策时需要考虑KRAS状态。

Objective:To compare the KRAS mutation of primary and liver metastasis tumors and explore the prognostic impact of KRAS mutation in patients underwent simultaneous resection for synchronous colorectal liver metastases(SCRLMs)that were initially resectable.Methods:Clinicopathological and outcome data of 139 consecutive patients with SCRLMs underwent simultaneous resection were collected.The KRAS genotype was evaluated in the primary cancer and liver metastasis tissues by Pyrosequencing.The prognostic value of KRAS status was assessed by Kaplan-Meier and Cox regression analyses.Results:The perioperative mortality was 0%,and the incidence of complications was 28.1%.KRAS mutated in 28.8%of the primary tumors of the SCRLMs patients,but the genotypes did not significantly associate with any clinicopathological characteristics.There was a high degree of consistency in KRAS mutation rates between primary(29.5%,28/95)and metastatic lesions(31.6%,30/95;P=0.157).Kaplan-Meier survival analysis showed that KRAS mutation was not significantly associated with overall survival(OS),but was significantly correlated with short disease-free survival(DFS,P=0.041).Multivariate survival analysis showed that KRAS mutation was an independent negative prognostic factor for DFS(P=0.012).Conclusions:KRAS mutation rate is highly consistent in primary and metastatic lesions,and correlated with DFS,so KRAS status should be taken into account when determining concurrent surgical decisions.