Comprehensive analysis reveals a prognostic and therapeutic biomarker CD3D in the breast carcinoma microenvironment

Abstract

Breast carcinoma (BRCA) is the most common carcinoma among women worldwide. Despite the great progress achieved in early detection and treatment, morbidity and mortality rates remain high. In the present study, we make a systematic analysis of BRCA using TCGA database by applying CIBERSORT and ESTIMATE computational methods, uncovered CD3D as a prognostic biomarker by intersection analysis of univariate COX and protein–protein interaction (PPI). It revealed that high CD3D expression was strongly associated with poor survival of BRCA, based on The Cancer Genome Atlas (TCGA) database and online websites. Gene Set Enrichment Analysis (GSEA) revealed that the high CD3D expression group was mainly enriched for the immune-related pathways and the low CD3D expression group was mainly enriched for metabolic-related activities. Based on CIBERSORT analysis, the difference test and correlation test suggested that CD3D had a strong correlation with T cells, particularly CD8 + T cells, which indicated that CD3D up-regulation may increase T cell immune infiltration in the TME and induce antitumor immunity by activating T lymphocytes. Furthermore, the correlation analysis showed that CD3D expression had a strongly positive correlation with immune checkpoints, which indicating that the underlying mechanism involves CD3D mediated regulation of T cell functions in BRCA, and single cell RNA-seq analysis revealed that CD3D correlate with CD8 + T cells and it is itself highly expressed in CD8 + T cells. In summary, we identified a prognostic biomarker CD3D in BRCA, which was associated with lymphocyte infiltration, immune checkpoints and could be developed for innovative therapeutics of BRCA.

CD3D Is an Independent Prognostic Factor and Correlates With Immune Infiltration in Gastric Cancer

“…have demonstrated that the CD3D/CD4 ratio was a stable independent prognostic factor in muscle-invasive bladder cancer ( 26 ). In addition, other studies have shown that high CD3D expression is strongly associated with poor survival in breast carcinoma ( 27 ). In contrast, in patients with colorectal cancer, high CD3D expression was found to predict better clinical outcomes ( 28 ).…”

A novel 4 immune-related genes as diagnostic markers and correlated with immune infiltrates in major depressive disorder

“…CD3D had an impact on the phenotype and in vitro function of immune cells. Previous study has showed that CD3D is closely related to glioblastoma multiforme [ 38 ], cervical cancer [ 39 ], and breast cancer [ 40 ]. Another study showed that CD3D was the target of mir-182-5p and might be used as candidate biomarkers of breast cancer [ 41 ].…”

CD3D: a prognostic biomarker associated with immune infiltration and immunotherapeutic response in head and neck squamous cell carcinoma

“…Moreover, Reyes-Gibby et al found that CD3Z was important for pretreatment pain in HNSCC patients [ 17 ]. Nevertheless, it has been reported that CD3D could be used as a favorable prognostic biomarker for both colon cancer and breast cancer [ 20 , 21 ], and the function of CD3D in HNSCC has yet to be completely elucidated. This research demonstrated that CD3D was overexpressed in HNSCC tissues compared with normal samples based on the TCGA database.…”

“…Yang et al suggested that CD3D could function as a prognostic marker for colon cancer and influence the development of immunotherapy [ 20 ]. According to Zhu et al, CD3D is a predictive biomarker of the prognosis of breast carcinoma associated with lymphocyte infiltration and immune checkpoints [ 21 ].…”