STAT3 and cancer: Ingenuity Upstream Regulator Analysis of the 25 high-classifier performance plasma sEV-associated proteins also identified in the cell line sEVs revealed the top upstream gene, RNA and protein regulators included AHR, VEGF, EGF, IL6, IRF1 and STAT3 (p = 1.22 × 10−7–3.45 × 10−6), consistent with plasma sEV representation of cancer-associated network mediators (Table A6A, Data S9).