Exosomal Del-1 as a Potent Diagnostic Marker for Breast Cancer: Prospective Cohort Study

• Published in: Clinical breast cancer 2021-12, Vol.21 (6), p.e748-e756
• Main Authors: Lee, Soo Jung, Lee, Jeeyeon, Jung, Jin Hyang, Park, Ho Yong, Moon, Pyong-Gon, Chae, Yee Soo, Baek, Moon-Chang
• Format: Article
• Language: English
• Subjects: Adult; Biomarker; Biomarkers, Tumor - blood; Blood-based biomarker; Breast Neoplasms - blood; Breast Neoplasms - diagnosis; Calcium-Binding Proteins - blood; Calcium-Binding Proteins - isolation & purification; Cell Adhesion Molecules - blood; Cell Adhesion Molecules - isolation & purification; Diagnostic biomarker; Early breast cancer; Enzyme-Linked Immunosorbent Assay; Exosome; Female; Humans; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prognosis; Prospective Studies; Risk Factors
• ISSN: 1526-8209; 1938-0666
• DOI: 10.1016/j.clbc.2021.02.002

The differential diagnostic role of plasma developmental endothelial locus-1 (Del-1) was proposed in our previous study. Therefore the current study aimed to confirm the diagnostic role and explore the prognostic role of exosomal Del-1 in a prospective cohort of female patients with breast cancer. To determine the optimal sampling time for the postoperative Del-1 measurements, blood was serially collected on days 1, 3, 5, and 7 after surgery in 22 patients (cohort 1). Thereafter, 111 female patients with breast cancer were prospectively enrolled (cohort 2) to compare exosomal Del-1 levels before and after surgery. Among the subsequent prospective cohort, 107 patients (96.4%) showed a high exosomal Del-1 level (optical density [OD] value > 0.5) at the time of diagnosis. Of these patients, 101 (94.6%) in this high-level group showed normalized Del-1 levels postoperatively, representing a significant difference (mean OD value, 1.232 vs. 0.196; P < .00001). High postoperative Del-1 level was significantly associated with a worse disease-free survival adjusted to the clinicopathological characteristics (hazard ratio, 24.0; P = .0011). This study confirmed the normalization of exosomal Del-1 after surgery, indicating exosomal Del-1 as a potent diagnostic biomarker for breast cancer. In addition, because a high Del-1 level after surgery was associated with early relapse, this suggests exosomal Del-1 as a potential prognostic marker by identifying the existence of residual cancer. Currently, there are no molecular biomarkers for the early detection of breast cancer. Our previous study identified surface proteins found on circulating exosomes for detecting early-stage breast cancer. In the current study, we aimed to confirm the diagnostic role of exosomal developmental endothelial locus-1 (Del-1) in a prospective cohort with breast cancer by comparing plasma exosomal Del-1 levels before and after curative surgery. This study confirmed the normalization of exosomal Del-1 after surgery, indicating exosomal Del-1 as a potent diagnostic biomarker for breast cancer. In addition, because a high Del-1 level after surgery was associated with early relapse, this suggests exosomal Del-1 as a potential prognostic marker by identifying the existence of residual cancer.