实用医学杂志 ›› 2021, Vol. 37 ›› Issue (21): 2748-2756.doi: 10.3969/j.issn.1006⁃5725.2021.21.009

• 临床研究 • 上一篇    下一篇

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

姚磊1 颜巍2 闫宇博1 郭元杰3 徐世东1   

  1. 哈尔滨医科大学附属肿瘤医院1 胸外科肺部病区,2 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)

  • 出版日期:2021-11-10 发布日期:2021-11-10
  • 通讯作者: 徐世东 E⁃mail:shidongxu@yahoo.cn
  • 基金资助:
    2018 黑龙江省博士后基金项目(编号:LBH⁃Z18156)

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

YAO Lei*,YAN Wei,YAM Yubo,GUO Yuanjie,XU Shidong   

  1. Department of Thoracic Surgery Affiliated Tumor Hospital of Harbin Medical University,Harbin150081,China 

  • Online:2021-11-10 Published:2021-11-10
  • Contact: XU Shidong E⁃mail:shidongxu@yahoo.cn

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 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 mutational burden,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+ 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。

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.

Abstract:

Objective To observe the TMB,immune infiltration and PD ⁃L1 expression in patients with gene⁃negative NSCLC after neoadjuvant immunotherapy,and analyze the prognostic factors. Methods 51 NSCLC patients 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 patients underwent neoadjuvant immunotherapy before surgical resection. High⁃throughput sequencing technology was used to detect the TMB of patients,anti⁃CD8 and anti⁃PD⁃L1 antibodies were used to detect immune infiltration and PD⁃L1 expression. The patients were followed up for up to 5 years,the PFS of the patients was recorded,and the Kaplan⁃Meier method was used to analyze the prognostic factors in patients with driver gene⁃negative NSCLC after neoadjuvant immunotherapy. Results The PFS between PD ⁃L1 positive patients(PD ⁃L1 +)and PD ⁃L1 negative patients(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 than others(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 were longer than others(P = 0.016 1). The PFS of TMB+ /CD8+ /PD⁃L1+ patients were longer than others(P = 0.037 7).Conclusion For operable NSCLC patients with negative driver genes,a comprehensive analysis of TMB,PD⁃L1 expression and immune infiltration is helpful to choice the treatment paln for patients.

Key words:

non ? small cell lung cancer, tumor mutation burden, neoadjuvant immunotherapy, Immune infiltration