K-Ras、BRAF、PIK3CA基因突变与直肠癌新辅助放化疗疗效及预后的关系  

Relationship between K-Ras,BRAF,PIK3CA gene mutation and the efficacy and prognosis of neoadjuvant chemoradiotherapy for rectal cancer

作　　者：张馨元 付永峰 白立立 杨森[1] 毛羽[1] 董立新[1] ZHANG Xinyuan;FU Yongfeng;BAI Lili;YANG Sen;MAO Yu;DONG Lixin(Department of Oncology,the First Hospital of Qinhuangdao,Hebei Qinhuangdao 066000,China.;Department of Plastic Surgery,the First Hospital of Qinhuangdao,Hebei Qinhuangdao 066000,China)

机构地区：[1]秦皇岛市第一医院肿瘤科,河北秦皇岛066000 [2]秦皇岛市第一医院烧伤整形美容外科,河北秦皇岛066000

出　　处：《现代肿瘤医学》2023年第16期3051-3055,共5页Journal of Modern Oncology

基　　金：河北省秦皇岛市科学技术研究与发展计划项目(编号:202004A049)。

摘　　要：目的:探讨K-Ras、BRAF、PIK3CA基因突变与直肠癌新辅助放化疗(nCRT)疗效及预后的关系。方法:选取2015年03月至2020年03月于医院接受nCRT并行根治手术的直肠癌患者182例作为研究对象。所有患者术前接受卡培他滨化疗,同时采用长程分割疗法进行放疗,共治疗5周,nCRT结束后5~12周,根据肿瘤位置及nCRT情况行手术治疗,出院后进行为期1年的随访。以肿瘤退缩分级(TRG)评价直肠癌nCRT疗效,TRG 1-3级纳入nCRT有效组,TRG 4-5级纳入nCRT无效组。nCRT前经肠镜取肿瘤组织,检测K-Ras、BRAF、PIK3CA基因突变状态,分析K-Ras、BRAF、PIK3CA基因突变与直肠癌nCRT疗效及预后的关系。结果:在182例直肠癌患者中,K-Ras、BRAF、PIK3CA基因突变率分别为34.07%、6.59%、13.19%,nCRT治疗有效率为60.44%。nCRT有效组K-Ras、BRAF及PIK3CA基因突变率显著低于nCRT无效组(P<0.05)。K-Ras、BRAF、PIK3CA基因突变状态预测直肠癌nCRT疗效的敏感度分别为68.45%、65.38%、57.76%,特异度分别为72.39%、69.23%、63.12%,AUC分别为0.626、0.573、0.532。Logistic回归分析结果显示K-Ras、BRAF、PIK3CA基因突变与直肠癌nCRT疗效显著相关(P<0.05)。K-Ras、BRAF、PIK3CA基因突变患者平均生存时间均分别短于K-Ras、BRAF、PIK3CA无突变者,差异有统计学意义(P<0.05)。多变量COX回归分析结果显示K-Ras、BRAF及PIK3CA基因突变患者死亡风险分别是K-Ras、BRAF、PIK3CA无突变者的1.639倍、1.811倍、1.432倍(P<0.05)。结论:K-Ras、BRAF、PIK3CA基因突变与直肠癌患者nCRT疗效和预后相关,可作为nCRT疗效和预后的预测指标。Objective:To investigate the relationship between K-Ras,BRAF,PIK3CA gene mutations and the efficacy and prognosis of neoadjuvant chemoradiotherapy(nCRT)for rectal cancer.Methods:From March 2015 to March 2020,182 rectal cancer patients who underwent nCRT and radical surgery in the hospital were selected as the research object.All patients received capecitabine chemotherapy before operation and long-term fractionated radiotherapy for 5 weeks.At 5~12 weeks after the end of nCRT,surgery was performed according to the tumor location and nCRT condition.After discharge,1-year follow-up was conducted.Tumor regression grade(TRG)was used to evaluate the efficacy of nCRT for rectal cancer.TRG grade 1-3 was included in the nCRT effective group,and TRG grade 4-5 was included in the nCRT ineffective group.Tumor tissues were taken by colonoscopy before nCRT,and the mutation status of K-Ras,BRAF and PIK3CA genes was detected.The relationship between K-Ras,BRAF and PIK3CA gene mutation and the curative effect and prognosis of rectal cancer nCRT was analyzed.Results:In 182 patients with rectal cancer,the mutation rates of K-Ras,BRAF and PIK3CA genes were 34.07%,6.59%and 13.19%respectively,and the effective rate of nCRT was 60.44%.The mutation rates of K-Ras,BRAF and PIK3CA genes in nCRT effective group were significantly lower than those in nCRT ineffective group(P<0.05).The sensitivity,specificity and AUC of K-Ras,BRAF and PIK3CA gene mutation in predicting the curative effect of nCRT in rectal cancer were 68.45%,65.38%,57.76%and 72.39%,69.23%,63.12%and 0.626,0.573,0.532,respectively.Logistic regression analysis showed that K-Ras,BRAF,PIK3CA gene mutations were significantly correlated with nCRT efficacy in rectal cancer(P<0.05).The average survival time of patients with K-Ras,BRAF and PIK3CA gene mutations was shorter than those without K-Ras,BRAF and PIK3CA mutations,respectively,and the difference was statistically significant(P<0.05).Multivariate COX regression analysis showed that the death risk of patients with K-Ras,BRAF a

关 键 词：直肠癌 新辅助放化疗 K-RAS BRAF PIK3CA 基因突变 疗效评估 预后 

分 类 号：R735.3[医药卫生—肿瘤]