Bioinformatics Analysis Of Chemokine And Tumor Infiltrating Immune Cells In Lung Adenocarcinoma

Objective:Lung adenocarcinoma(LUAD)is the most common malignany.Currently,accumulating evidences have demonstrated that immune infiltration acts a key role in the tumorigenesis of LUAD.Moreover,chemokines modulate tumor immunity,thus affecting therapeutic effect and the prognosis of LUAD patients.Therefore,the purpose of this study was to identify the chemokines associated with immune infiltration as prognostic biomarkers of LUAD patients.Methods:We downloaded the transcriptome expression profiles and clinical information of LUAD patients from The Cancer Genome Atlas(TCGA)database.We use CIBERSORT algorithm to calculate fractions of 22 immune cells.The overall survival(OS)of patients were performed using Kaplan-Meier(K-M)analysis based on the expression of immune cells.We also observed the correlations between differentially expressed chemokines and immune cells in LUAD using Tumor Immune Estimation Resource(TIMER)and tumor-immune system interactions(TISIDB)databases.Functional enrichment analyses of these chemokines were conducted by cluster Profiler R package.In addition,PPI network was constructed by the Search Tool for the Retrieval of Interacting Gene(STRING)database to screen the hub genes.Finally,survival analyses of hub genes were performed to evaluate the prognostic value in the development of LUAD.Results:The fractions of 22 immune cells significantly varied between the tumor and normal groups.Compared with normal group,LUAD patients contained a lower fraction of na(?)ve B cells?Plasma cells?CD4+follicular helper T cells?regulatory T cells.We also found that differentially expressed chemokines were correlated with tumor infiltrating immune cells.Functional enrichment analysis revealed that these chemokines were mainly enriched in response to chemokine,cytokine activity,and chemokine signaling pathway.Furthermore,CXCL9 and CXCL10 were identified as hub genes,and the expression of CXCL9 and CXCL10 showed significant correlations with the survival in pathological Stage of LUAD patients.The expression levels of CXCL9 and CXCL10 in LUAD patients were strongly associated with the disease survival rate.Conclusion:Collectively,all results suggest that CXCL9 and CXCL10 of chemokines associated with tumor infiltrating immune cells may act as prognostic markers in LUAD.