A Somatic Mutation Signature Predicts the Best Overall Response to Anti-programmed Cell Death Protein-1 Treatment in Epidermal Growth Factor Receptor/Anaplastic Lymphoma Kinase-Negative Non-squamous Non-small Cell Lung Cancer

Frontiers in Medicine

article

Jie Peng¹  Lushan Xiao²  Dan Zou¹  Lijie Han³ 

[1] Department of Medical Oncology, The Second Affiliated Hospital, Guizhou Medical University;Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University;Department of Hematology, The First Affiliated Hospital of Zhengzhou University

关键词: non-small cell lung cancer;    anti-PD-1;    best overall response;    somatic mutations;    EGFR/ALK negative;   

DOI  :  10.3389/fmed.2022.808378

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background We aimed to exploit a somatic mutation signature (SMS) to predict the best overall response to anti-programmed cell death protein-1 (PD-1) therapy in non-small cell lung cancer (NSCLC). Methods Tumor samples of 248 patients with epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)-negative non-squamous NSCLC treated with anti-PD-1 were molecularly tested by targeted next-generation sequencing or whole exome sequencing. On the basis of machine learning, we developed and validated a predictive model named SMS using the training ( n = 83) and validation ( n = 165) cohorts. Results The SMS model comprising a panel of 15 genes ( TP53, PTPRD, SMARCA4, FAT1, MGA, NOTCH1, NTRK3, INPP4B, KMT2A, PAK1, ATRX, BCOR, KDM5C, DDR2 , and ARID1B ) was built to predict best overall response in the training cohort. The areas under the curves of the training and validation cohorts were higher than those of tumor mutational burden and PD-L1 expression. Patients with SMS-high in the training and validation cohorts had poorer progression-free survival [hazard ratio (HR) = 6.01, P < 0.001; HR = 3.89, P < 0.001] and overall survival ( HR = 7.60, P < 0.001; HR = 2.82, P < 0.001) than patients with SMS-low. SMS was an independent factor in multivariate analyses of progression-free survival and overall survival ( HR = 4.32, P < 0.001; HR = 3.07, P < 0.001, respectively). Conclusion This study revealed the predictive value of SMS for immunotherapy best overall response and prognosis in EGFR/ALK-negative non-squamous NSCLC as a potential biomarker in anti-PD-1 therapy.

【 授权许可】

CC BY