Biophysical Parameters of Plasma-Derived Extracellular Vesicles as Potential Biomarkers of Bone Disturbances in Breast Cancer Patients Receiving an Individualized Nutrition Intervention.

Extracellular vesicles (EVs) are implicated in several biological conditions, including bone metabolism disturbances in breast cancer patients (BCPs). These disorders hinder the adjustment of nutrition interventions due to changes in bone mineral density (BMD). The biophysical properties of EVs (e.g., size or electrostatic repulsion) affect their cellular uptake, however, their clinical relevance is unclear. In this study, we aimed to investigate the association between the biophysical properties of the plasma-derived EVs and BMDs in BCPs who received an individualized nutrition intervention during the first six months of antineoplastic treatment. As part of the nutritional assessment before and after the intervention, body composition including bone densitometry and plasma samples were obtained. In 16 BCPs, EVs were isolated using ExoQuick® and their biophysical properties were analyzed using light-scattering techniques. We found that the average hydrodynamic diameter of large EVs was associated with femoral neck bone mineral content, lumbar spine BMD, and neoplasms' molecular subtypes. These results provide evidence that EVs play a role in BCPs' bone disorders and suggest that the biophysical properties of EVs may serve as potential nutritional biomarkers. Further studies are needed to evaluate EVs' biophysical properties as potential nutritional biomarkers in a clinical context.

Extracellular Vesicles and Their Zeta Potential as Future Markers Associated with Nutrition and Molecular Biomarkers in Breast Cancer.

A nutritional intervention promotes the loss of body and visceral fat while maintaining muscle mass in breast cancer patients. Extracellular vesicles (EVs) and their characteristics can be potential biomarkers of disease. Here, we explore the changes in the Zeta potential of EVs; the content of miRNA-30, miRNA-145, and miRNA-155; and their association with body composition and biomarkers of metabolic risk in breast cancer patients, before and 6 months after a nutritional intervention. Clinicopathological data (HER2neu, estrogen receptor, and Ki67), anthropometric and body composition data, and plasma samples were available from a previous study. Plasma EVs were isolated and characterized in 16 patients. The expression of miRNA-30, miRNA-145, and miRNA-155 was analyzed. The Zeta potential was associated with HER2neu (ß = 2.1; p = 0.00), Ki67 (ß = -1.39; p = 0.007), estrogen positive (ß = 1.57; p = 0.01), weight (ß = -0.09; p = 0.00), and visceral fat (ß = 0.004; p = 0.00). miRNA-30 was associated with LDL (ß = -0.012; p = 0.01) and HDL (ß = -0.02; p = 0.05). miRNA-155 was associated with visceral fat (ß = -0.0007; p = 0.05) and Ki67 (ß = -0.47; p = 0.04). Our results reveal significant associations between the expression of miRNA-30 and miRNA-155 and the Zeta potential of the EVs with biomarkers of metabolic risk and disease prognosis in women with breast cancer; particularly, the Zeta potential of EVs can be a new biomarker sensitive to changes in the nutritional status and breast cancer progression.