Volume 29, Issue 3
DOI: 10.24205/03276716.2020.954
Comprehensive analysis of CD2 in the immune microenvironment of breast cancer
Abstract
Background: Tumor microenvironment is essential for breast cancer progression and metastasis. Our study sets out to examine the genes affecting stromal and immune infiltration in breast cancer progression and prognosis. Methods: This work provides an approach for quantifying stromal and immune scores by using the ESTIMATE algorithm based on the gene expression matrix of breast cancer patients in the TCGA database. We found differentially expressed genes (DEGs) through the limma R package. Functional enrichments were accessed through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Besides, we constructed a protein-protein network, identified several key genes in Cytoscape. Through univariate COX analysis and online website Kaplan-Meier plotter analysis, genes significantly related to prognosis were determined. Their level of expression was determined through an online database (TIMER; HPA). Furthermore, their relationship with infiltrating immune cells was evaluated by Tumor IMmune Estimation Resource (TIMER) web tool. A prognosis analysis based on the expression levels of CD2 was further performed in related immune cells subgroup. Result: To better understand the relationship between immune and stromal cell-related genes and prognosis, we screened patients with breast cancer in The Cancer Genome Atlas (TCGA) database and divided them into high and low groups based on immune/stromal scores. Immune score results showed that the high score subgroup was significantly associated (p = 0.008) with a better prognosis. Differential gene identification results show that there are 473 up-regulated genes and 49 down-regulated genes. Functional analysis of DEGs revealed their potential functions in immune response and extracellular interaction. Ten related prognostic genes were identified through univariate COX analysis and PPI network analysis. Multiple online databases have verified their expression levels, and the results show that CD2 is significantly high in tumors. We found that in the BRCA, CD2 was positively correlated with B cells (cor = 0.552), CD4 T cells (cor = 0.679), CD8 T cells (cor = 0.595), neutrophils (cor = 0.653) and dendritic cells (cor = 0.728). The expression level of CD2 was also correlated with related immune cells subgroup. On the whole, further research on CD2 can reveal a new understanding of the potential relationship between tumor microenvironment and breast cancer prognosis
Keywords
breast cancer, tumor microenvironment, immune infiltration, The Cancer Genome Atlas