1196 Circulating extracellular vesicles of patients with melanoma differ in concentration and composition compared to healthy controls

Melanoma is the most aggressive skin cancer and is responsible for the majority of skin cancer deaths. Despite advances in treatment, our current prognostic indicators are poor and fail to adequately risk-stratify our patients. This study evaluates the concentration, size, proteomic and metabolomic profile of circulating extracellular vesicles (EVs) isolated from the plasma of patients with melanoma, to identify potential biomarkers of disease and progression. This clinical cohort =study recruited n=36 patients with melanoma and n=13 healthy controls and isolated the EVs from their plasma using a clinically applicable technique - Size Exclusion Chromatography (SEC). EVs were then characterized according to the Minimal Information for Studies of Extracellular Vesicles guidelines (2018). Nanoparticle Tracking analysis demonstrated an increase in the concentration of EVs isolated from the plasma of patients with melanoma in comparison to healthy controls (p=0.002), though no significant difference in the concentration between those with primary and metastatic melanoma. No significant difference was detected in the modal size or protein concentration of EVs between groups. Proteomic profiling robustly identified over 300 proteins within the EVs and 88 metabolites, with variations in profiles demonstrated between those with metastatic and primary disease, and compared to healthy controls. This work further supports the potential role of EVs as diagnostic biomarkers in melanoma and gives insight into the targets for further study.