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

TLDR

Extracellular vesicles released by cancer cells can serve as biomarker sources, and fibronectin is a promising candidate because it is present on EVs from breast cancer cell lines. The study aimed to evaluate fibronectin on circulating EVs as a liquid biopsy for early breast cancer detection. Researchers applied two ELISA assays to measure fibronectin on EVs in plasma from healthy controls, breast cancer patients, post‑surgery patients, benign breast tumor patients, and patients with non‑cancerous diseases. Fibronectin on EVs was significantly elevated in all breast cancer stages, returned to normal after tumor removal, and yielded superior diagnostic accuracy (AUC 0.81, 65 % sensitivity, 83 % specificity) compared with plasma fibronectin (AUC 0.77, 69 % sensitivity, 73 % specificity).

Abstract

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.