Analysis Of Differential Genes That Affect The Efficacy Of Nivolumab And Pembrolizumab In The Treatment Of Non-small Cell Lung Cancer Based On GEO Database

Objective:Using gene expression chip database and bioinformatics methods to screen the differential genes that affect the efficacy of Nivolumab and Pembrolizumab in the treatment of Non-small cell lung cancer(NSCLC),providing references for the selection and prognosis of these two commonly used immunotherapy drugs in clinical practice.Methods:Searching the GEO database for "Nivolumab" and "Pembrolizumab" to find the target chip,downloading the immunotherapy-related expression chip “GSE93157”,screening out a total of 35 Non-small cell lung cancer related samples,using the R language data packages to analyze the expression of differential genes in the samples and the cluster analysis of different differential genes.Gene function annotation GO analysis and KEGG pathway analysis of differential genes were performed on the Metascape,then screen immune-related genes through Imm Port,and the protein-protein interaction network was constructed using String and Cytoscape software.The plug-in Cytohubba in Cytoscape software was used to identify the pivot genes through the MCC method,and the Kaplan-Meier plotter database was used to perform survival analysis on the pivot genes to determine the key genes that affect different anti-programmed cell death protein 1 drug treatments.The relationship between the genetic variation and expression of genes common to the two drugs and the pathological stage and pathological characteristics of NSCLC was analyzed.Results:1.Through the analysis of differential genes in Non-small cell lung cancer patients with different therapeutic effects of Nivolumab or Pembrolizumab(clinical benefits and disease progression),a total of 58 differential genes were screened that affect the efficacy of Nivolumab therapy,including 25 immune-related genes;There are 231 differential genes and 82 immune-related genes that affect the efficacy of Pembrolizumab.2.These differential genes are involved in different biological processes.The cell components involved in the significant enrichment of Nivolumab’s differential gene GO function are mainly: MHC protein complex and membrane raft;the biological processes involved are lymphocyte activation,adaptive immune response,leukocyte differentiation,and regulation of B cell activation,negative regulation of immune system processes,etc.The KEGG pathway involved is enriched in Th17 cell differentiation,cytokine and cytokine receptor interaction,primary immunodeficiency,B cell receptor signaling pathway,T cell receptor signaling pathway,etc.The GO function analysis of differential genes related to Pembrolizumab enriches the main cell components including the external side of plasma membrane and receptor complex;biological processes include lymphocyte activation,positive regulation of cytokine production,cytokine receptor binding,positive regulation of defense response,leukocyte activation involved in immune response,leukocyte migration,etc.The KEGG pathway involved is enriched for cytokine-cytokine receptor interaction,Jak-STAT signaling pathway,Th17 cell differentiation,TNF signaling pathway,NF-kappa B signaling pathway,Natural killer cell mediated cytotoxicity,Toll-like receptors signaling pathway,etc.3.The protein-protein interaction network based on two kinds of drug immune-related differential genes suggests that a total of 2 sub-networks are obtained for Nivolumab,with a total of 11 nodes and 51 edges for the main module;A total of 4sub-networks for Pembrolizumab,with a total of 24 main modules Nodes,231 edges.4.The survival analysis of the top 10 main immune-related genes that affect the efficacy of the two drugs was performed,and the genes with statistically significant differences in survival(p<0.05)were selected.The results showed that the Immune-related differential genes to Nivolumab were CD5 and CD22,CR2,CD40 LG.The Immune-related differential genes to Pembrolizumab are CTLA4,SELL,IL7,CD40 LG,CD2,IL7 R.The high expression of these genes in patients with Non-small cell lung cancer suggests a poor prognosis,and the overall survival period is significantly shorter than that of patients with low gene expression.5.CD40 LG has different degrees of genetic changes in NSCLC,including missense mutations,truncating mutations,amplification and so on.6.The expression of CD40 LG in stage Ⅰ NSCLC is higher than that in stage Ⅱ NSCLC(p<0.05).The expression in stage Ⅲ and Ⅳ was not significantly higher than that in phase Ⅱ.In lung adenocarcinoma,the expression of CD40 LG was correlated with T stage,N stage,M stage,age,race,and ethnicity(p<0.05).In lung squamous cell carcinoma,the expression of CD40 LG is related to T stage(p<0.05),and N stage,M stage,age,race and ethnicity have no correlation.Conclusion:Through bioinformatics analysis,the key immune-related differential genes for Nivolumab in the treatment of NSCLC patients are CD5,CD22,CR2,and CD40LG;the key immune-related differential genes for Pembrolizumab in the treatment of NSCLC patients are CTLA4,SELL,IL7,CD2,IL7 R,CD40LG.The differential gene related to the common immunity of the two drugs is CD40 LG,and the expression of CD40 LG is related to T stage.These key immune-related differential genes are expected to become potential biomarkers and targets for predicting the efficacy of anti-PD-1inhibitors in the treatment of NSCLC patients.