Background: Tumor mutation burden (TMB) is novel biomarker of promising predict value in prediction of immune checkpoint inhibitors (ICPis) in non-small cell lung cancer (NSCLC). However, the distribution of TMB in epidermal growth factor receptor (EGFR)-mutant advanced lung adenocarcinoma (LUAD) patients and the impact on overall survival (OS) time are not well demonstrated.
Methods: Information regarding gene mutations and patients' survival time in advanced LUAD was downloaded from The Cancer Genome Atlas (TCGA) database. The diversity of TMB in different EGFR-mutant types was observed and the predicted value of TMB for OS as well as other co-mutations were analyzed. The diversity of TMB was also observed in another Chinese cohort of advanced LUAD patients.
Results: The median TMB values of EGFR wild-type, other types of EGFR mutations, exon 19 deletions and L858R were 6.12, 5.66, 3.77 and 4.72, differences between wild-type and EGFR sensitive mutations (exon 19 deletion or L858R) were significant (P<0.001 and P<0.01). OS time of high TMB group was inferior to that of the low TMB group (24.03 months vs. not reached, P=0.0020). TMB and TP53 together will make more accurate prediction of OS in EGFR-mutant advanced LUAD patients. Distribution of TMB in another Chinese cohort had the same trend.
Conclusions: In advanced LUAD patients, TMB was lower in patients with EGFR-mutant group than EGFR wild group. TMB was a negative prognostic biomarker of OS in EGFR-mutant LUAD patients, especially when TP53 was mutated together.
Keywords: Lung adenocarcinoma (LUAD); epidermal growth factor receptor mutation (EGFR mutation); overall survival (OS); prognosis; tumor mutation burden (TMB).
2019 Journal of Thoracic Disease. All rights reserved.