title: Identification of Developmental Endothelial Locus-1 on Circulating Extracellular Vesicles as a Novel Biomarker for Early Breast Cancer Detection.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Pyong-Gon
authors.initials: PG
authors.lastname: Moon
authors.affiliation: Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Cho
authors.affiliation: Department of Oncology/Hematology, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Breast and Thyroid Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Jin Hyang
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Department of Oncology/Hematology, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Yee Soo
authors.initials: YS
authors.lastname: Chae
authors.affiliation: Department of Pathology, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Han-Ik
authors.initials: HI
authors.lastname: Bae
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Young-Bum
authors.initials: YB
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Breast and Thyroid Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Ho Yong
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. mcbaek@knu.ac.kr.
authors.forename: Moon-Chang
authors.initials: MC
authors.lastname: Baek
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay; D000067128:Extracellular Vesicles / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D040901:Proteomics / Q000379:methods; D012372:ROC Curve; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C110183:EDIL3 protein, human