Profiling of extracellular vesicles of metastatic urothelial cancer patients to discover protein signatures related to treatment outcome.

Abstract

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 plasma-isolated 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 SYND-1. We found, no association between EVs/ml plasma at baseline and progression-free survival (PFS). Protein profiling of EVs, using an antibody-based 92-plex Proximity Extension Assay on the Oncology II® platform, revealed a heterogeneous protein expression pattern. Qlucore bioinformatic analyses put forward a protein signature comprising of SYND-1, TNFSF13, FGF-BP1, TFPI-2, 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 FR-alpha, 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.

• Authors: Kristina Viktorsson, Petra Hååg, Carl-Henrik Shah, Bo Franzén, Vasiliki Arapi, Karin Holmsten, Per Sandström, Rolf Lewensohn, Anders Ullén
• Journal: Molecular oncology (Mol Oncol) Vol. 16 Issue 20 Pg. 3620-3641 (Oct 2022) ISSN: 1878-0261 [Electronic] United States
• PMID: 35838333 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Chemical References

• Sorafenib
• Toll-Like Receptor 3
• Biomarkers

Topics

• Humans
• Carcinoma, Transitional Cell (metabolism, pathology)
• Sorafenib (pharmacology, therapeutic use)
• Toll-Like Receptor 3 (metabolism)
• Urinary Bladder Neoplasms (pathology)
• Extracellular Vesicles (metabolism)
• Biomarkers (metabolism)
• Treatment Outcome