Abstract 1738P
Background
Lung cancer has always been a high incidence of malignant tumor. Immune checkpoint inhibitors (ICIs) including atezolizumab, pembrolizumab have shown durable responses and have been approved by FDA. However, ICIs demonstrate antitumor effects only in a fraction of patients, and research exploring the association between gene mutation and clinical benefit is limited. ZNF479 (encoding zinc finger protein 479) mutation rate is high in lung cancer. Studies have shown that lymphoid and myeloid expressed different sets of the expression of ZNF479 and other closely related genes, which means that ZNF479 may be related to immunity. But the association between ZNF479 mutation and survival in lung cancer is unknown.
Methods
Genomic and survival data of lung cancer patients administrated with ICIs was retrieved from publicly accessible data (Miao2018.Pancancer.249.WES).The association between ZNF479 mutation with PFS and OS was analyzed using Kaplan-Meier curves and log-rank tests. The association between ZNF479 mutation with TMB (Tumor Mutation Burden) was also analyzed in this cohort, Wilcoxon test was used for the comparison of TMB. In addition, genomic and immune cell infiltration data of 517 patients with Lung Adenocarcinoma was obtained from TCGA. The correlation analysis between immune cell infiltration and ZNF479 mutation status was further analyzed by CIBERSORT-ABS. Statistical significance was set at p=0.05.
Results
10.5% (6/57) lung cancer patients in the clinical cohort harbored ZNF479 mutation. ZNF479 mutation is associated with higher TMB (p=0.044), significantly longer PFS(16.0 vs 4.2 months; HR, 0.1; P=0.006) and longer OS (23.3 vs 6.8 months; p=0.032) in lung cancer patients treated with ICIs. Furthermore, the correlation analysis between immune infiltration and ZNF479 mutation status shows that M1 macrophages, CD8 T cells increased significantly (p=0.017, p=0.035) while the Myeloid dendritic cells decreased significantly (p=0.034).
Conclusions
This study shows that ZNF479 mutation may serve as a potential positive biomarker of ICIs in lung cancer since it correlated with higher TMB, up regulation of M1 macrophages, CD8 T cells and down regulation of Myeloid dendritic cells.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
D. Fan: Financial Interests, Personal and Institutional, Member: 3DMed. Inc. Y. Chen: Financial Interests, Personal and Institutional, Member: 3DMed. Inc. M. Huang: Financial Interests, Personal and Institutional, Member: 3DMed. Inc. All other authors have declared no conflicts of interest.