Relationship Between Tumor Mutation Burden And Clinicopathological And Molecular Characteristics In Advanced Non-small Cell Lung Cancer

Objective:To study the relationship between clinical characteristics and tumor mutation burden(TMB)level in patients with advanced non-small cell lung cancer(NSCLC),to study the relationship between molecular characteristics and TMB level in patients with advanced NSCLC,to analyze the influence of TMB level on patients with advanced NSCLC,and to explore the clinical significance of TMB.Methods:64 cases of the second hospital and the third hospital of Jilin university between August 2017 and November 2020 were retrospectively analyzed.They were detected the level of TMB,9 common drive gene(EGFR,ALK,ROS-1,KRAS,MET,RET,HER2,mutated BRAF,NTRK)and 8 common non-drive gene(TP53,APC,RUNX1,ASXL,PIK3CA,PTEN,ZNF217,RB1)in the second generation sequencing method.Patients with different TMB levels were grouped according to different research backgrounds to study their pathological and molecular characteristics.Based on the data provided by the gene detection company,the patients in the study who ranked in the top 1/4 of the NSCLC patient database with TMB mutations(ranking value≤25%)were classified as the high TMB group,and the patients who ranked in the>25%were classified as the low TMB group.SPSS 25.0 statistical software was used for statistical analysis.Pearsonχ~2,continuous correctedχ~2,Fisher’s accurate test,Kaplan-Meier survival estimate,Cox proportional hazards model,linear regression and other methods were used to test the results.Bilateral P<0.05 was considered statistically significant.Results:1.General situation:(1)Non-smoking(P=0.012)and adenocarcinoma(P=0.038)were associated with lower TMB levels of advanced NSCLC.(2)There was no statistical significance between different levels of TMB and the incidence of metastasis in different sites.There was no significant difference in the driver gene mutation under different TMB levels.(3)In the range of 8 non-driver gene mutations included in the study,patients with low TMB levels had a higher incidence of single non-driver gene mutations than multiple genes.(4)Simultaneous mutations in multiple non-driver genes,including TP53(P=0)or APC(P=0.022)mutations,were more common in patients with high TMB.2.Among advanced squamous cell carcinoma patients,PIK3CA gene mutation was more likely to occur in NSCLC patients with high TMB level(P=0.048).3.Among advanced adenocarcinoma patients,RB1 mutations were more common in patients with high levels of TMB(P=0.001),while there was no statistically significant difference between driver gene mutations and other 7non-driver gene mutations in the study range at different TMB levels.4.In patients with advanced NSCLC,patients with TP53 mutations(P=0.026)may have elevated TMB levels.5.In univariate analysis,the median PFS was not significantly prolonged in patients with high TMB compared with those with low TMB(10m vs 7.0m,P=0.235).In multivariate analysis,the survival data of PFS in women(P=0.036)and patients with EGFR mutation(P=0.019)were better than those in men and patients without EGFR mutation.Conclusion:1.The clinical characteristics of patients with advanced NSCLC are correlated with TMB level to a certain extent,and non-smoking patients with lung adenocarcinoma are more likely to have low TMB level.2.There was no significant correlation between driver gene mutations and TMB level in patients with advanced NSCLC,and non-driver gene mutations such as TP53,APC and RUNX1 were more likely to occur alone in patients with low TMB level.3.Simultaneously mutated non-driver genes,including TP53 or APC mutations,are more common in patients with advanced NSCLC with high TMB levels.4.Among patients with advanced NSCLC squamous cell carcinoma,patients with high TMB level are more likely to have PIK3CA gene mutation.5.In patients with advanced NSCLC adenocarcinoma,patients with high TMB level are more likely to have RB1 gene mutation.6.Mutation of TP53 gene can lead to elevated TMB level.7.TMB level did not affect PFS in patients with advanced NSCLC,and women and those with EGFR mutations were more likely to achieve better PFS survival.