驱动基因阴性非小细胞肺癌患者新辅助免疫治疗手术后预后的影响因素  

Analysis the prognostic factors in patients with driver gene-negative NSCLC after neoadjuvant immunotherapy

作　　者：姚磊[1] 颜巍[2] 闫宇博 郭元杰 徐世东[1] YAO Lei;YAN Wei;YAM Yubo;GUO Yuanjie;XU Shidong(Department of Thoracic Surgery,Affiliated Tumor Hospital of Harbin Medical University,Harbin150081,China;不详)

机构地区：[1]哈尔滨医科大学附属肿瘤医院胸外科肺部病区,哈尔滨150081 [2]哈尔滨医科大学附属肿瘤医院消毒供应中心,哈尔滨150081 [3]阿勒泰地区人民医院胸外科,新疆阿勒泰836500

出　　处：《实用医学杂志》2021年第21期2748-2751,2756,共5页The Journal of Practical Medicine

基　　金：2018黑龙江省博士后基金项目(编号:LBH-Z18156)。

摘　　要：目的观察可手术切除的驱动基因阴性非小细胞肺癌患者(non small cell lung cancer,NSCLC)的肿瘤突变负荷(tumor mutational burden,TMB)、免疫浸润和PD-L1表达情况,分析NSCLC患者新辅助免疫治疗手术预后的影响因素。方法收集并追溯2015年以来在哈尔滨医科大学附属肿瘤医院就医的NSCLC患者共51例,所有患者穿刺肺组织经肺癌9合1试剂盒检测为驱动基因阴性者,且患者在手术切除之前进行了新辅助免疫治疗。利用高通量测序技术检测患者的肿瘤突变负荷(tumor mutationalburden,TMB),抗CD8和抗PD-L1抗体检测免疫浸润和PD-L1表达情况。对患者进行最多长达5年的随访,记录患者的无进展生存期(progression-free survival,PFS),利用Kaplan-Meier方法分析NSCLC患者新辅助免疫治疗手术预后的影响因素。结果 PD-L1阳性组(PD-L1^(+))和PD-L1阴性组(PD-L1^(+))患者的无进展生存期差异无统计学意义(P=0.461 1);TMB高突变组(TMB^(+))无进展生存期比TMB低突变组(TMB^(+))更长(P=0.004 7);CD8阳性组(CD8^(+))无进展生存期比CD8阴性组(CD8^(+))更长(P=0.001 4);PD-L1^(+)/TMB^(+)患者较其他患者无进展生存期更长(P=0.001 9);PD-L1^(+)/TMB^(+)患者和其他患者无进展生存期差异无统计学意义(P=0.361 1);CD8^(+)/TMB^(+)患者较其他患者无进展生存期更长(P=0.036 9);CD8^(+)/PD-L1^(+)患者较其他患者无进展生存期更长(P=0.016 1);TMB^(+)/CD8^(+)/PD-L1^(+)患者较其他患者无进展生存期更长(P=0.037 7)。结论对于驱动基因阴性的可手术的NSCLC患者,综合分析TMB、PD-L1表达和免疫浸润情况有助于选择对患者的治疗方案。bjective To observe the TMB,immune infiltration and PD-L1 expression in patients withgene-negative NSCLC after neoadjuvant immunotherapy,and analyze the prognostic factors.Methods 51 NSCLCpatients from the Affiliated Tumor Hospital of Harbin Medical University since 2015 were collected and retrospective.The driver gene of lung tissue punctured patients were negative by the 9-in-1 lung cancer test kit,and the patientsunderwent neoadjuvant immunotherapy before surgical resection.High-throughput sequencing technology was usedto detect the TMB of patients,anti-CD8 and anti-PD-L1 antibodies were used to detect immune infiltration andPD-L1 expression.The patients were followed up for up to 5 years,the PFS of the patients was recorded,and theKaplan-Meier method was used to analyze the prognostic factors in patients with driver gene-negative NSCLC afterneoadjuvant immunotherapy.Results The PFS between PD-L1 positive patients(PD-L1^(+))and PD-L1 negativepatients(PD-L1^(+))had no significant difference(P=0.461 1).The PFS of TMB high mutation patients(TMB^(+))were longer than TMB low mutation patients(TMB^(+))(P=0.004 7).The PFS of CD8 positive patients(CD8^(+))were longer than CD8 negative patients(CD8^(+))(P=0.001 4).The PFS of PD-L1^(+)/TMB^(+)patients were longer thanothers(P=0.001 9).The PFS between PD-L1^(+)/TMB^(+)patients and others had no significant difference(P=0.361 1).The PFS of CD8^(+)/TMB^(+)patients were longer than others(P=0.036 9).The PFS of CD8^(+)/PD-L1^(+)patients werelonger than others(P=0.016 1).The PFS of TMB^(+)/CD8^(+)/PD-L1^(+)patients were longer than others(P=0.037 7).

关 键 词：非小细胞肺癌 肿瘤突变负荷 新辅助免疫治疗 免疫浸润 

分 类 号：R734.2[医药卫生—肿瘤]