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Purpose: Currently, there are no molecular biomarkers for the early detection of breast cancer. This study focused on identifying surface proteins found on circulating extracellular vesicles (EVs) for detecting early-stage breast cancer.Experimental Design: Circulating EVs, isolated from the plasma of 10 patients with breast cancer (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 ELISAs were used to measure Del-1 in plasma samples from healthy controls (n = 81), patients with breast cancer (n = 269), breast cancer patients after surgical resection (n = 50), patients with benign breast tumors (n = 64), and patients with noncancerous diseases (n = 98) in two cohorts.Results: Plasma Del-1 levels were significantly higher (P < 0.0001) in patients with breast cancer than in all controls and returned to almost normal after tumor removal. The diagnostic accuracy of Del-1 was AUC, 0.961 [95% confidence interval (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 breast cancer by one type of ELISA. Furthermore, Del-1 maintained diagnostic accuracy for patients with early-stage breast cancer 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 breast cancer and distinguish breast cancer from benign breast tumors and noncancerous diseases. Clin Cancer Res; 22(7); 1757–66. ©2015 AACR. |
