Unraveling exosomal cargo for kidney cancer diagnostics Small extracellular vesicles with large implications

Open Access
Authors
  • R.C. Zieren
Supervisors
  • H.P. Beerlage
  • A.D. Bins
Cosupervisors
  • P.J. Zondervan
  • K.J. Pienta
Award date 10 November 2026
ISBN
  • 9789465379753
Number of pages 315
Organisations
  • Faculty of Medicine (AMC-UvA)
Abstract

The aim of this thesis is to provide guidance to cliniciansand biomedical scientists on the value of non-invasive biomarkers for renalcancer diagnosis through the development of improved extracellular vesicle (EV)methodology and the discovery of candidate biomarkers.
Part I Development of methods for EV enrichment
Chapter 2 addresses the latest technical advancements in the enrichmentand detection of EVs and examines their application as diagnostic, prognostic,and therapeutic biomarkers in prostate, bladder, and renal cancers. Chapter3 compares four methods, i.e. ultracentrifugation, chemical precipitation,size-exclusion chromatography, and a microfluidic tangential flow filtrationdevice, for EV enrichment from human plasma, urine, and cultured cancer cells. Chapter4 details the validation of assays for EV enrichment from human renalcancer tissue and adjacent benign renal tissue, adhering to standards set bythe International Society for Extracellular Vesicles. Chapter 5 utilizeshigh-throughput simultaneous mRNA profiling technology to compare mRNAtranscripts in EVs from cultured cells.
Part II Diagnostic RCC biomarker discovery
Chapter 6 proposes potential biomarkers identified through the analysisof mRNA and proteins in EVs derived from cultured renal cancer and benign renalcells. Chapter 7 compares mRNA transcripts in EVs from matched urine,renal cancer tissue, and adjacent benign renal tissue in patients with renalcancer, identifying potential biomarkers.
Part III General discussion and summary
The thesis concludes with a general discussion and future perspectives (Chapter8), followed by summaries in English (Chapter 9) and Dutch (Chapter10).
Document type PhD thesis
Note Please note that the 'About the author' and 'Acknowledgements' sections are not included in the thesis downloads.

Chapter 1: This version of the article has been accepted for publication, after peer review but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1038/s41585-023-00818-y. Use of this Accepted Version is subject to the publisher’s Accepted Manuscript terms of use https://www.springernature.com/gp/open-research/policies/acceptedmanuscript-terms
Language English
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