Identification of Developmental Endothelial Locus-1 on Circulating Extracellular Vesicles as a Novel Biomarker for Early Breast Cancer Detection
A partir d'échantillons sanguins prélevés sur 10 patientes atteintes d'un cancer du sein de stade I ou II et sur 5 témoins, cette étude coréenne suggère l'intérêt de mesurer le niveau de la protéine Del-1, exprimée à la surface de vésicules extracellulaires, pour le diagnostic précoce de la maladie
Purpose Currently, there are no molecular biomarkers for the early detection of breast cancer (BC). This study focused on identifying surface proteins found on circulating extracellular vesicles (EVs) for detecting early-stage BC.
Experimental Design Circulating EVs, isolated from the plasma of 10 patients with BC (stages I and II), and 5 healthy controls, were analyzed using LC-MS/MS. Developmental endothelial locus-1 protein (Del-1) was selected as a candidate biomarker. Two different enzyme-linked immunosorbent assays (ELISAs) were used to measure Del-1 in plasma samples from healthy controls (n = 81), patients with BC (n = 269), BC patients after surgical resection (n = 50), patients with benign breast tumors (n = 64), and patients with non-cancerous diseases (n = 98), in two cohorts.
Results Plasma Del-1 levels were significantly higher (P < 0.0001) in patients with BC than in all controls and returned to almost normal after tumor removal. The diagnostic accuracy of Del-1 was area under the curve (AUC), 0.961 [95% CI, 0.924-0.983], sensitivity of 94.70% and specificity of 86.36% in test cohort, and 0.968 [0.933-0.988], 92.31% and 86.62% in validation cohort for early-stage BC by one type of ELISA. Furthermore, Del-1 maintained diagnostic accuracy for patients with early-stage BC using the other type of ELISA (0.946 [0.905-0.972], 90.90%, and 77.14% in the test cohort; 0.943 [0.900-0.971], 89.23%, and 80.99% in the validation cohort).
Conclusions Del-1 on circulating EVs is a promising marker to improve identification of patients with early-stage BC and distinguish BC from benign breast tumors and non-cancerous diseases.
Clinical Cancer Research , résumé, 2015