Proteomic exploration of the plasma EV compartment revealed differentially expressed proteins that offer circulating evidence of tumorigenic reprogramming including proteins related to altered metabolism (GLUD1, ALDH1L1, BHMT) [17–19], protein fate and trafficking (HUWE1, EXOC8, NCCRP1) [20–23], cytoskeletal remodeling (TPM3) [24], transcriptional regulation (HIST1H4A, MED14) [25, 26] and tumor stemness (SRGN) [27]. The gene discussed is HUWE1; the disease is neoplasm.