Del-1 Expression as a Potential Biomarker in Triple-Negative Early Breast Cancer

Abstract

Objective: A differential diagnostic role for plasma Del-1 was proposed for early breast cancer (EBC) in our previous study. We examined tumoral Del-1 expression and analyzed its prognostic impact among patients with EBC. Methods: Del-1 mRNA expression was assessed in breast epithelial and cancer cells. Meanwhile, the tumoral expression of Del-1 was determined based on tissue microarrays and immunohistochemistry results from 440 patients. Results: While a high Del-1 mRNA expression was found in all the breast cancer cell lines, the expression was significantly higher in MDA-MB-231. Tumoral expression of Del-1 was also significantly associated with a negative expression of estrogen receptor or progesterone receptor, and low expression of Ki-67, particularly in the case of triple-negative breast cancer (TNBC) (p < 0.036). Furthermore, a correlation was found between Del-1 expression and an aggressive histological grade, nuclear mitosis, and polymorphism, suggesting a possible role in tumor progression. In the survival analysis, a worse distant disease-free survival trend was noted for the group overexpressing Del-1. Conclusion: While all the investigated breast cancer cell lines exhibited Del-1 expression, the expression rate and intensity were specifically prominent in TNBC. In addition, based on its relationship to an unfavorable histology and worse survival trend, Del-1 could act as a molecular target in TNBC patients.

EDIL3 promotes epithelial–mesenchymal transition and paclitaxel resistance through its interaction with integrin αVβ3 in cancer cells

“…In this study, we demonstrated a significant association between EDIL3 protein expression and Gleason score in prostate cancer. We also found an association between EDIL3 protein expression and tumor grade in breast cancer, as previously reported 23 , and to explore the correlation between EDIL3 expression and overall survival of the patients, we studied the TCGA database where we analyzed the RNAseq in breast cancer patients 28 . We observed a statistical significance in the group of patients with high levels of mRNA of EDIL3 that had a shorter overall survival at 10 years, in a Kaplan–Meier’s survival curve.…”

“…EDIL3 acts as a pro-angiogenic factor, mediator of the immune and anti-inflammatory response, and a regulator of endothelial cell adhesion and migration [13][14][15] . It has been reported that EDIL3 is overexpressed in several tumor types, including bladder, pancreas, breast, and liver carcinomas, and associates with tumor progression and poor prognosis [16][17][18][19][20][21][22][23] . EDIL3 has been identified as a novel regulator of EMT in hepatocellular carcinoma cells, as the increased expression of EDIL3 by miRNA-137 downregulation triggers ERK and TGF-β activation via interaction with the integrin α V β 3 ( 20 ).…”

“…This integrin plays a crucial role in the growth of brain metastasis in breast cancer 24 . Also, EDIL3 has been identified in the extracellular vesicles of breast cancer cells that may be used for early breast cancer detection in the plasma of patients [21][22][23][24][25] .…”

Tumor derived EDIL3 modulates the expansion and osteoclastogenesis of myeloid derived suppressor cells in murine breast cancer model

“…In breast cancer, EDIL3 is associated with the diagnosis and outcome of patients. High expression of EDIL3 is related to early breast cancer with worse survival trend, especially in triple-negative breast cancer(TNBC) [32], [33], [34]. Moreover, EDIL3 secreted by cellular ingredients of hematopoietic stem cells (HSCs) niche is indispensable to myelopoiesis in both physiologic and pathologic conditions [35].…”

EDIL3 is a novel regulator epithelial-mesenchymal transition in Clear Cell Renal Cell Carcinoma: In silico analysis

“…Moreover, EDIL3 has shown to induce EMT in many types of tumor tissues (10)(11)(12)(13)(14). It is overexpressed during the transition from kidney intraepithelial neoplasia to invasive carcinoma and lead to significant increase in proliferation, angiogenesis, invasion and metastasis capacity (15).…”