Affordable Access

Access to the full text

Defining candidate mRNA and protein EV biomarkers to discriminate ccRCC and pRCC from non-malignant renal cells in vitro

  • Zieren, Richard C.1, 2
  • Dong, Liang1, 3
  • Clark, David J.4
  • Kuczler, Morgan D.1
  • Horie, Kengo1
  • Moreno, Leandro Ferreira5
  • Lih, Tung-Shing M.4
  • Schnaubelt, Michael4
  • Vermeulen, Louis5
  • Zhang, Hui4
  • de Reijke, Theo M.2
  • Pienta, Kenneth J.1
  • Amend, Sarah R.1
  • 1 Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA , Baltimore (United States)
  • 2 Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 3 Shanghai Jiao Tong University School of Medicine, Shanghai, China , Shanghai (China)
  • 4 The Johns Hopkins University, Baltimore, MD, 21287, USA , Baltimore (United States)
  • 5 Oncode Institute, Amsterdam UMC, Amsterdam, The Netherlands , Amsterdam (Netherlands)
Published Article
Medical Oncology
Publication Date
Jul 31, 2021
DOI: 10.1007/s12032-021-01554-2
Springer Nature
  • Original Paper


Renal cell carcinoma (RCC) accounts for over 400,000 new cases and 175,000 deaths annually. Diagnostic RCC biomarkers may prevent overtreatment in patients with early disease. Extracellular vesicles (EVs) are a promising source of RCC biomarkers because EVs carry proteins and messenger RNA (mRNA) among other biomolecules. We aimed to identify biomarkers and assess biological functions of EV cargo from clear cell RCC (ccRCC), papillary RCC (pRCC), and benign kidney cell lines. EVs were enriched from conditioned cell media by size exclusion chromatography. The EV proteome was assessed using Tandem Mass Tag mass spectrometry (TMT-MS) and NanoString nCounter technology was used to profile 770 cancer-related mRNA present in EVs. The heterogeneity of protein and mRNA abundance and identification highlighted the heterogeneity of EV cargo, even between cell lines of a similar pathological group (e.g., ccRCC or pRCC). Overall, 1726 proteins were quantified across all EV samples, including 181 proteins that were detected in all samples. In the targeted profiling of mRNA by NanoString, 461 mRNAs were detected in EVs from at least one cell line, including 159 that were present in EVs from all cell lines. In addition to a shared EV cargo signature, pRCC, ccRCC, and/or benign renal cell lines also showed unique signatures. Using this multi-omics approach, we identified 34 protein candidate pRCC EV biomarkers and 20 protein and 8 mRNA candidate ccRCC EV biomarkers for clinical validation.

Report this publication


Seen <100 times