CD40LG as a prognostic molecular marker regulates tumor microenvironment through immune process in breast cancer

Abstract

Purpose: Breast cancer (BRCA) is the second most common malignancy in the world and the most common in women. Here, we utilized publicly available BRCA dataset to inves-tigate potential prognosis-related genes through integrated bioinformatics analysis. Materials and Methods: BRCA dataset was obtained from the Cancer Genome Atlas (TCGA) database. The ESTIMATE algorithm was used to calculate the ImmuneScores and StromalScores of the samples and then divided them into high-and low-score groups based on the median score. Common differentially expressed genes (DEGs) were identified through differential expression analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The core prognostic genes were the intersection of hub genes from PPI network and prognostic genes from univariate Cox proportional hazard regression analysis. Finally, the CIBERSORT algorithm was used to calculate proportions of 22 tumor-infiltrating immune cells (TICs) in BRCA samples. Results: A total of 486 DEGs were identified. These genes were mainly enriched in immune-related pathways. Crossover genes between the hub genes and the prognostic genes were CD2 and CD40LG. CD40LG was further investigated in this study. CD40LG was downregulated in BRCA samples compared with normal samples, and a lower CD40LG expression was associated with advanced tumor stages and a poor prognosis. CD40LG was shown to be involved in immune-related pathways of BRCA by Gene Set Enrichment Analysis. Finally, 14 TICs were found to have a close relationship with CD40LG. Conclusion: CD40LG was found to be a core prognostic gene related to tumor microenvironment and deeply involved in immune-related pathways in BRCA. Our findings may provide new insights for exploring the molecular mechanisms of BRCA and developing new immunotherapies for the disease.