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

Chong Yuan; Kaili Chang; Chenyue Xu; Qingquan Li; Zunguo Du

doi:10.1016/j.tranon.2021.101080

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

Transl Oncol. 2021 Jul;14(7):101080. doi: 10.1016/j.tranon.2021.101080. Epub 2021 Apr 26.

Authors

Chong Yuan¹, Kaili Chang¹, Chenyue Xu¹, Qingquan Li², Zunguo Du³

Affiliations

¹ Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
² Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: 061101040@fudan.edu.cn.
³ Department of pathology, Huashan hospital, Fudan university, No.12 Middle Urumqi road, Shanghai 200032, China. Electronic address: duzunguo@126.com.

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; Immune infiltration; Invasive breast cancer; P53 signaling pathway; Prognosis biomarker.