Exploration Of The Relationship Between Tumor Mutation Burden, Prognosis And Immune Infiltration In Non-small Cell Lung Cancer

Background and purpose:In a variety of malignant tumors,it is still controversial whether tumor mutation burden(TMB)is related to survival outcomes or the promotion of immunotherapies.In recent years,tumor mutation burden has played an important role in the evaluation of the efficacy of lung cancer immunotherapy,but its specific mechanism and how to regulate the changes of tumor microenvironment are still not clearly reported.This article uses bioinformatics data to summarize and analyze the effect of TMB on the prognosis of non-small cell lung cancer(NSCLC),and further explore the relationship between TMB and immune cell infiltration.Methods:The somatic gene mutation data,transcriptome data and clinical data of 1016 NSCLC patients were downloaded from The Cancer Genome Atlas(TCGA)database,and the mutation profiles were analyzed using the R language "maftools" software package,and the TMB of each sample was calculated.We divided these samples into a high TMB group and a low TMB group,and conducted a survival analysis of the two groups.The “limma” software package was used to conduct a differential analysis of the expression profiles between the two groups and we abtained differently expressed genes.Based on the ImmPort database,we selected 16 differentially expressed genes related to immunity.In batch survival analysis,we identified genes related to survival outcomes.Based on TIMER database,we further evaluated the association of these genes with immune cell infiltration in NSCLC.Finally,Cox regression and survival analysis were used to evaluate the prognostic value of immune cells.Results:The survival analysis of the two groups suggested that the survival rate of patients in the high TMB group was worse than that in the low TMB group.Among the 16 differentially expressed genes obtained,16 immune-related key genes were selected based on ImmPort database.We identified 4 prognosis-related genes from batch survival analysis.Immune cell infiltration analysis and survival analysis showed that lower immune cell infiltration was negatively correlated with the prognosis of lung adenocarcinoma.Conclusion:1.For patients with NSCLC,people with low TMB have better survival than those with high TMB.2.A higher TMB in lung adenocarcinoma is associated with poorer survival outcomes,which may be related to its suppression of immune cell infiltration in the tumor.3.There are 16 differentially expressed genes between the high and low TMB groups of NSCLC patients,including A2ML1,CALCA,DEFB132,DEFB107 A,DEFB127,DEFB128,IFNK,MMP12,MUC5 AC,NTS,PGC,PI3,PTHLH,RORC,S100A2,S100A7.4.In 16 genes which are both differentially expressed in the high and low TMB groups and related to immunity,the high expression of DEFB132,DEFB107 A,DEFB127,DEFB128 is negatively correlated with poor prognosis.5.In lung adenocarcinoma,patients with lower B cell and dendritic cell infiltration have poor survival results.