Development and validation of a genomic mutation signature to predict response to PD-1 inhibitors in non-squamous NSCLC: a multicohort study
Development and validation of a genomic mutation signature to predict response to PD-1 inhibitors in non-squamous NSCLC: a multicohort study
复制标题
开发和验证基因组突变特征以预测非鳞状 NSCLC 对 PD-1 抑制剂的反应：一项多队列研究
DOI：
10.1136/jitc-2019-000381
复制
发表时间：
2020-01-01
影响因子：
10.9
通讯作者：
Dong, Zhong-Yi
中科院分区：
文献类型：
--
作者：
Bai, Xue;Wu, De-Hua;Dong, Zhong-Yi
Background Genetic variations of some driver genes in non-small cell lung cancer (NSCLC) had shown potential impact on immune microenvironment and associated with response or resistance to programmed cell death protein 1 (PD-1) blockade immunotherapy. We therefore undertook an exploratory analysis to develop a genomic mutation signature (GMS) and predict the response to anti-PD-(L)1 therapy. Methods In this multicohort analysis, 316 patients with non-squamous NSCLC treated with anti-PD-(L)1 from three independent cohorts were included in our study. Tumor samples from the patients were molecularly profiled by MSK-IMPACT or whole exome sequencing. We developed a risk model named GMS based on the MSK training cohort (n=123). The predictive model was first validated in the separate internal MSK cohort (n=82) and then validated in an external cohort containing 111 patients from previously published clinical trials. Results A GMS risk model consisting of eight genes (TP53,KRAS,STK11,EGFR,PTPRD,KMT2C,SMAD4, andHGF) was generated to classify patients into high and low GMS groups in the training cohort. Patients with high GMS in the training cohort had longer progression-free survival (hazard ratio (HR) 0.41, 0.28-0.61, p
