CD2 Is a Novel Immune-Related Prognostic Biomarker of Invasive Breast Carcinoma That Modulates the Tumor Microenvironment

Abstract

Female breast cancer (BCa) is the most commonly occurring cancer worldwide. The tumor microenvironment (TME) plays an essential role in tumor invasion, angiogenesis, unlimited proliferation, and even immune escape, but we know little about the TME of BCa. In this study, we aimed to find a TME-related biomarker for BCa, especially for invasive breast carcinoma (BRCA), that could predict prognosis and immunotherapy efficacy. Based on RNA-seq transcriptome data and the clinical characteristics of 1222 samples (113 normal and 1109 tumor samples) from The Cancer Genome Atlas (TCGA) database, we used the ESTIMATE algorithm to calculate the ImmuneScore and StromalScore and then identified differentially expressed genes (DEGs) between the high and low ImmuneScore groups and the high and low StromalScore groups. Thereafter, a protein–protein interaction (PPI) network analysis and univariate Cox regression analyses of overall survival were used to identify potential key genes. Five candidate genes were identified, comprising CD2, CCL19, CD52, CD3E, and ITK. Thereafter, we focused on CD2, analyzing CD2 expression and its association with survival. CD2 expression was associated with tumor size (T stage) to some extent, but not with overall TNM stage, lymph node status (N stage), or distant metastasis (M stage). High CD2 expression was associated with longer survival. METABRIC data were used to validate the survival result (n = 276). Gene set enrichment analysis (GSEA) showed that the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were significantly associated with high CD2 expression were mainly immune-related pathways. Furthermore, CD2 expression was correlated with 16 types of tumor-infiltrating immune cells (TICs). Hence, CD2 might be a novel biomarker in terms of molecular typing, and it may serve as a complementary approach to TNM staging to improve clinical outcome prediction for BCa patients.

CD40LG as a Prognostic Molecular Marker Regulates Tumor Microenvironment Through Immune Process in Breast Cancer

“…The intersecting genes between the prognostic genes and the hub genes were CD2 and CD40LG ( Figure 4C ). Because CD2 had been a known prognostic genes in BRCA, 12 , 14 we herein focused on CD40LG for further investigation.

Figure 4 Core prognostic genes analysis.

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“… 11 In addition, Chen et al and Wang et al respectively revealed that CD2 and CD52 were two immune-related prognostic factor in BRCA via regulating TME. 12 , 13 With similar approach, we identified another prognostic gene that was deeply involved in the immune and TME regulation of BRCA through an integrated bioinformatic analysis.…”

A Novel Immune and Stroma Related Prognostic Marker for Invasive Breast Cancer in Tumor Microenvironment: A TCGA Based Study

“…Interestingly, CD2 was considered a prognostic biomarker in a previous study due to the strong correlation with OS. The possible reason for this contradiction may be that they did not consider the clinical factors ( 20 ). In addition, the BC samples were grouped into ITK high-expression and low-expression groups compared with the ITK median expression.…”

Immune Infiltration of MMP14 in Pan Cancer and Its Prognostic Effect on Tumors

“…Common and important immune cells include neutrophils, natural killer cells, macrophages, dendritic cells, B cells, and T cells. In the TME, various immune factors are regulated by various key factors while playing their roles (58)(59)(60). Moreover, an increasing number of studies have shown that immune cells play important roles in the occurrence and development of many tumors (61)(62)(63).…”