Identification of developmental endothelial locus-1 on circulating extracellular vesicles as a novel biomarker for early breast cancer detection

Pyong Gon Moon, Jeong Eun Lee, Young Eun Cho, Soo Jung Lee, Jin Hyang Jung, Yee Soo Chae, Han Ik Bae, Young Bum Kim, In-San Kim, Ho Yong Park, Moon Chang Baek

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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 ELISAswere used tomeasureDel-1 in plasma samples fromhealthy 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.

Original languageEnglish
Pages (from-to)1757-1766
Number of pages10
JournalClinical Cancer Research
Volume22
Issue number7
DOIs
Publication statusPublished - 2016 Apr 1
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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