Exosome-derived Developmental Endothelial Locus-1 as a novel diagnostic marker for breast cancer.

e22262 Background: Extracellular vesicles (EVs) or exosomes were recently identified to participate in intercellular communication through exosomal proteins or RNAs suggesting its potential role in cancer development and progression. Therefore, the current study focused to identify exosomal proteins from plasma of breast cancer patients and evaluated their role for breast cancer. Methods: The developmental endothelial locus-1 protein (Del-1) was identified and selected as a biomarker candidate by analyzing circulating EVs isolated from plasma of 10 patients with early breast cancer (stages I and II) and 5 disease-free individuals using LC-MS/MS. A subsequent study analyzed derived Del-1 in plasma samples from normal subjects (n = 81), patients with breast cancer (n = 269), patients who underwent removal of a breast tumor (n = 50), patients with benign breast tumor (n = 64), and patients with non-cancerous diseases (thyroiditis, gastritis, hepatitis B, and rheumatoid arthritis; n = 99) by using two different ELISA methods. Plus, a duplication study was performed in a different cohort (n = 242) to confirm its role in breast cancer. Results: ExosomalDel-1 level was significantly elevated (P < .0001) in patients at all stages of breast cancer compared with normal controls or patients with benign diseases, and moreover returned to normal after tumor removal. The area under receiver operating characteristic curve (AUC) was 0.99 (95% CI, 0.98 to 0.99) providing sensitivity of 76.8% and specificity of 90.2%, which was similar in both the early-stage BC and all BC patients. Plus, the diagnostic value of these exosomal Del-1 was reconfirmed in an independent validation cohort. Conclusions: Our findings showDel-1 on circulating EVs could improve identification of patients with early breast cancer thereby suggesting exosomal Del-1 as a possible biomarker for early detection of breast cancer in particular for high-risk subjects or breast cancer patients who underwent curative surgery.