In the present study, we examined the expression of MMP-2, MMP-9, terminal compliment complex (C5b-9), and VEGF-A in the crown of circulating sEVs in patients with recurrent and recurrence-free GBM in correlation with the molecular portrait of the primary tumor to identify a combination of promising markers for use in cancer diagnosis and prognosis using liquid biopsy. Here, MMP2 is linked to glioblastoma.