Screening And Functional Analysis Of CD40LG As A Prognostic Marker In Breast Cancer Based On Bioinformatics

Purpose: Screening and functional analysis of novel prognostic markers related to tumor microenvironment in breast cancer.Methods: A dataset containing breast cancer tumor samples and paracancer samples was obtained from the publicly available database TCGA.The Immune/Stromal/ESTIMATE Scores of each breast cancer sample were calculated by the ESTIMATE algorithm though the R software,and the samples were divided into high and low score groups based on the median of each type of score.R software "survival" and "survminer" program package were used for survival analysis of patients of each type of score.The correlation between the scores and clinicopathological features of patients were analyzed though R software "ggpubr" program package.The common differentially expressed genes between high and low score groups were obtained though R software "limma","Venn Diagram" program package.R software "survival" program package was used to identify the prognostic genes among the DEGs.The PPI network was constructed with the common differentially expressed genes,and the genes with top 10 neighboring nodes were core genes.The crossover gene between the prognostic genes and core genes was selected as the core prognostic gene in breast cancer microenvironment.The differential expression level of the core prognostic gene was compared,and the correlation between the overall survival,PAM50 molecular subtypes and clinicopathological features with the core prognostic gene were also analyzed.Finally,GSEA analysis and CIBERSORT algorithm were used to explore the enrichment pathways and immunological functions of the core prognostic gene.Results: The overall survival of patients in the high-Immune Score group was significantly higher than that in the low-Immune Score group（p=0.023）,but not in the Stromal Score and ESTIMATEScore group（p=0.431,p=0.174）.A total of 486 differentially expressed genes were screened in breast cancer microenvironment,among which CD40 LG and CD2 were the core prognostic genes.The expression of CD40 LG in tumor tissue was significantly lower than that in normal tissue（p<0.001）.In Luminal B and Her-enriched breast cancer,overall survival was significantly higher in patients with high CD40 LG expression than those with low CD40 LG expression（p<0.001,p=0.045）,but there was no significant difference in Luminal A type（p=0.872）,basal-like type（p=0.605）and Normal breast-like type（p=0.134）breast cancer.In GSEA analysis,the high expression CD40 LG group was mainly enriched in immune and inflammatory pathways,while the low expression CD40 LG group was mainly enriched in substance metabolism and energy conversion.In the breast cancer microenvironment,the content of 8 kinds of immune cells were positively correlated with the expression level of CD40 LG,while 6 kinds of immune cells were negatively correlated with the expression level of CD40 LG.Conclusion: CD40 LG is a prognostic marker of breast cancer and may be involved in the progression of breast cancer through multiple immune pathways in tumor microenvironment.