The prognosis of metastatic urothelial carcinoma (mUC) patients is poor, and early prediction of systemic therapy response would be valuable to improve outcome. In this exploratory study, we investigated protein profiles in sequential plasmaâisolated extracellular vesicles (EVs) from a subset of mUC patients treated within a Phase I trial with vinflunine combined with sorafenib. The isolated EVs were of exosome size and expressed exosome markers CD9, TSG101 and SYNDâ1. We found, no association between EVs/ml plasma at baseline and progressionâfree survival (PFS). Protein profiling of EVs, using an antibodyâbased 92âplex Proximity Extension Assay on the Oncology II
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platform, revealed a heterogeneous protein expression pattern. Qlucore bioinformatic analyses put forward a protein signature comprising of SYNDâ1, TNFSF13, FGFâBP1, TFPIâ2, GZMH, ABL1 and ERBB3 to be putatively associated with PFS. Similarly, a protein signature from EVs that related to best treatment response was found, which included FRâalpha, TLR 3, TRAIL and FASLG. Several of the markers in the PFS or best treatment response signatures were also identified by a machine learning classification algorithm. In conclusion, protein profiling of EVs isolated from plasma of mUC patients shows a potential to identify protein signatures that may associate with PFS and/or treatment response.