EGFR共突变状态对晚期肺腺癌患者预后的价值研究  

Prognostic value of EGFR co-mutation status in patients with advanced lung adenocarcinoma

作　　者：袁胜芳 任婕 林卫佳 姬泽萱 张长洪[1] 王布[1] Yuan Shengfang;Ren Jie;Lin Weijia;Ji Zexuan;Zhang Changhong;Wang Bu(Department of Respiratory and Critical Care Medicine,First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,China)

机构地区：[1]河北北方学院附属第一医院呼吸与危重症医学科,张家口075000

出　　处：《国际肿瘤学杂志》2024年第9期556-562,共7页Journal of International Oncology

摘　　要：目的探讨表皮生长因子受体(EGFR)共突变状态对晚期肺腺癌患者预后的价值。方法前瞻性收集2019年1月至2022年12月就诊于河北北方学院附属第一医院呼吸与危重症医学科首次确诊的ⅢB~Ⅳ期肺腺癌患者的临床资料。根据EGFR是否合并其他基因突变,将患者分为EGFR突变组(n=82)和EGFR共突变组(n=74)。采用实时荧光定量PCR法测定外周血循环肿瘤DNA(ctDNA)水平。比较两组客观缓解率(ORR)、疾病控制率(DCR)、患者治疗前及治疗1个月后外周血ctDNA水平、无进展生存期(PFS)。采用Cox比例风险回归模型行单因素和多因素分析。结果EGFR突变组中EGFR19缺失突变45例,EGFR21点突变37例;EGFR共突变组中EGFR19缺失突变41例,EGFR21点突变33例,合并TP53突变46例、RB1突变16例、PTEN突变6例、MET扩增2例,ERBB2突变、KRAS突变、RET重排、ALK重排各1例。EGFR突变组和EGFR共突变组肿瘤最大径(χ^(2)=5.04,P=0.025)、分期(χ^(2)=3.92,P=0.048)差异均有统计学意义。两组ORR分别为64.63%(53/82)、37.84%(28/74),差异有统计学意义(χ^(2)=11.19,P<0.001);DCR分别为96.34%(79/82)、86.49%(64/74),差异有统计学意义(χ^(2)=4.95,P=0.026)。EGFR突变组和EGFR共突变组治疗1个月后ctDNA水平均较治疗前有所降低[2.63(1.83,3.30)ng/μl比4.73(3.92,5.49)ng/μl,Z=-7.06,P<0.001;4.26(2.26,6.07)ng/μl比5.28(4.37,6.09)ng/μl,Z=-5.15,P<0.001],治疗前及治疗1个月后EGFR共突变组ctDNA水平均较EGFR突变组升高(Z=-2.47,P=0.013;Z=-4.29,P<0.001)。EGFR共突变组中,靶向治疗有效患者治疗1个月后外周血ctDNA水平较治疗前有所降低[(2.03±0.63)ng/μl比(3.92±0.82)ng/μl,t=42.94,P<0.001],治疗前及治疗1个月后无效患者外周血ctDNA水平均高于有效患者[(5.84±0.57)ng/μl比(3.92±0.82)ng/μl,t=-11.91,P<0.001;(5.87±1.64)ng/μl比(2.03±0.63)ng/μl,t=-14.43,P<0.001]。EGFR突变组、EGFR共突变组患者中位PFS分别为10.4、8.3个月,差异有统计学意义(χ^(2)=22.28,P<0.001)。Objective To explore the prognostic value of epidermal growth factor receptor(EGFR)co-mutation status in patients with advanced lung adenocarcinoma.Methods Clinical data of patients with stageⅢB-Ⅳlung adenocarcinoma who were first diagnosed in the Department of Respiratory and Critical Care Medicine,First Affiliated Hospital of Hebei North University from January 2019 to December 2022 were collected prospectively.Patients were divided into EGFR mutation group(n=82)and EGFR co-mutation group(n=74)according to whether EGFR was combined with other gene mutations.The level of circulating tumor DNA(ctDNA)in peripheral blood was measured by real time fluorescence quantitative PCR.Objective response rate(ORR),disease control rate(DCR),the levels of ctDNA in peripheral blood,and progression-free survival(PFS)were compared between two groups of patients before and after 1 month of treatment.The univariate and multivariate analyses were conducted by Cox proportional hazards regression model.Results In the EGFR mutation group,there were 45 cases of EGFR19 deletion mutation and 37 cases of EGFR21 mutation.In the EGFR co-mutation group,there were 41 cases of EGFR19 deletion mutation,33 cases of EGFR21 mutation,46 cases of TP53 mutation,16 cases of RB1 mutation,6 cases of PTEN mutation,2 cases of MET amplification,1 case of ERBB2 mutation,1 case of KRAS mutation,1 case of RET rearrangement,and 1 case of ALK rearrangement.There were statistically significant differences between the EGFR mutation group and the EGFR co-mutation group in the maximum tumor diameter(χ^(2)=5.04,P=0.025)and stage(χ^(2)=3.92,P=0.048).The ORRs of the two groups were 64.63%(53/82)and 37.84%(28/74),respectively,with a statistically significant difference(χ^(2)=11.19,P<0.001).The DCRs were 96.34%(79/82)and 86.49%(64/74),respectively,with a statistically significant difference(χ^(2)=4.95,P=0.026).The ctDNA levels in the EGFR mutation group and EGFR co-mutation group after one month of treatment decreased compared to before treatment[2.63(1.83,3.30)n

关 键 词：肺腺癌 基因 erbB-1 循环肿瘤DNA 预后 

分 类 号：R734.2[医药卫生—肿瘤]