Extracellular vesicle proteome of breast cancer patients with and without cognitive impairment following anthracycline-based chemotherapy

Cognitive impairment due to cancer and its therapy is a major concern among cancer survivors. Extracellular vesicles (EVs) composition altered by cancer and chemotherapy may affect neurological processes such as neuroplasticity, potentially impacting the cognitive abilities of cancer survivors. We investigated the EV proteome of breast cancer patients with and without cognitive impairment following anthracycline-based chemotherapy from longitudinally collected plasma. EVs were cup-shaped and positive for Flotillin-1 and TSG-101. We identified 517 differentially expressed EV proteins between the cognitive impaired and non-impaired groups during and post-chemotherapy. The observed decreased expression of p2X purinoceptor, cofilin-1, ADAM 10, and dynamin-1 in the plasma EVs of cognitive impaired group may suggest alterations in mechanisms underlying synaptic plasticity. The reduced expression of tight junction proteins among cognitive-impaired patients may imply weakening of the blood-brain barrier. These EV protein signatures may serve as a fingerprint that underscore the mechanisms underlying cognitive impairment in cancer survivors.