4.3 Article

Fibronectin on circulating extracellular vesicles as a liquid biopsy to detect breast cancer

Journal

ONCOTARGET
Volume 7, Issue 26, Pages 40189-40199

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9561

Keywords

breast cancer; diagnosis; extracellular vesicle; ELISA

Funding

  1. National Research Foundation of Korea (NRF) - Ministry of Science, ICT and future Planning [NRF-2015R1A2A2A01007711, 2014R1A5A2009242]
  2. Ministry of Health & Welfare, Republic of Korea [HI12C0534]
  3. Ministry of Health and Welfare, Republic of Korea [1420390]

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Extracellular vesicles (EVs) secreted from cancer cells have potential for generating cancer biomarker signatures. Fibronectin (FN) was selected as a biomarker candidate, due to the presence in surface on EVs secreted from human breast cancer cell lines. A subsequent study used two types of enzyme-linked immunosorbent assays (ELISA) to determine the presence of these proteins in plasma samples from disease-free individuals (n=70), patients with BC (n=240), BC patients after surgical resection (n=40), patients with benign breast tumor (n=55), and patients with non-cancerous diseases (thyroiditis, gastritis, hepatitis B, and rheumatoid arthritis; n=80). FN levels were significantly elevated (p<.0001) at all stages of BC, and returned to normal after tumor removal. The diagnostic accuracy for FN detection in extracellular vesicles (ELISA method 1) (area under the curve, 0.81; 95% CI, 0.76 to 0.86; sensitivity of 65.1% and specificity of 83.2%) were also better than those for FN detection in the plasma (ELISA method 2) (area under the curve, 0.77; 95% CI, 0.72 to 0.83; sensitivity of 69.2% and specificity of 73.3%) in BC. The diagnostic accuracy of plasma FN was similar in both the early-stage BC and all BC patients, as well as in the two sets. This liquid biopsy to detect FN on circulating EVs could be a promising method to detect early breast cancer.

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