High expression of DLL3 is associated with a poor prognosis and immune infiltration in invasive breast cancer patients

Abstract

Background: Previous studies have shown the prognostic value of delta like canonical Notch ligand 3 (DLL3) in patients with different types of tumors, but the role and predictive value of DLL3 in invasive breast cancer (IBC) have not been reported. In this study, we explored the prognostic ability and potential ways of DLL3 in IBC patients. Methods: We retrospectively enrolled 130 IBC patients from a single institution from 2004 to 2019 for bioinformatics and statistical analysis. The Cancer Genome Atlas breast invasive carcinoma (TCGA-BRCA) cohort was used for verification. Results: High expression of DLL3 was associated with overall survival (OS) in IBC patients (P = 0.023). Multivariate analysis further showed that DLL3 expression was an independent prognostic factor (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.01–1.15; P = 0.017). Time-dependent receiver operating characteristic (ROC) with the area under the curve (0.786) demonstrated that DLL3 expression can predict the survival outcome of IBC patients. Furthermore, the expression of DLL3 was related to a variety of tumor infiltrating immune cells (TIICs), particularly T cells regulatory (Tregs). Gene set enrichment analysis (GSEA) and immunohistochemistry (IHC) results indicated that DLL3 was closely related to p53 signaling pathway. Conclusions: High expression of DLL3 was associated with poor prognosis and immune cell infiltration in IBC patients. Moreover, P53 signaling pathway may be the key pathway.

Keywords

• Delta like canonical Notch ligand 3
• Invasive breast cancer
• Prognosis biomarker
• P53 signaling pathway
• Immune infiltration