Large Extracellular Vesicle Characterization and Association with Circulating Tumor Cells in Metastatic Castrate Resistant Prostate Cancer

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Liquid biopsies hold potential as minimally invasive sources of tumor biomarkers for diagnosis, prognosis, therapy prediction or disease monitoring. We present an approach for parallel single-object identification of circulating tumor cells (CTCs) and tumor-derived large extracellular vesicles (LEVs) based on automated high-resolution immunofluorescence followed by downstream multiplexed protein profiling. Identification of LEVs >6 µm in size and CTC enumeration was highly correlated, with LEVs being 1.9 times as frequent as CTCs, and additional LEVs were identified in 73% of CTC-negative liquid biopsy samples from metastatic castrate resistant prostate cancer. Imaging mass cytometry (IMC) revealed that 49% of cytokeratin (CK)-positive LEVs and CTCs were EpCAM-negative, while frequently carrying prostate cancer tumor markers including AR, PSA, and PSMA. HSPD1 was shown to be a specific biomarker for tumor derived circulating cells and LEVs. CTCs and LEVs could be discriminated based on size, morphology, DNA load and protein score but not by protein signatures. Protein profiles were overall heterogeneous, and clusters could be identified across object classes. Parallel analysis of CTCs and LEVs confers increased sensitivity for liquid biopsies and expanded specificity with downstream characterization. Combined, it raises the possibility of a more comprehensive assessment of the disease state for precise diagnosis and monitoring.

Detaljer

Författare
  • Anna Sandström Gerdtsson
  • Sonia M Setayesh
  • Paymaneh D Malihi
  • Carmen Ruiz
  • Anders Carlsson
  • Nevarez Rafael
  • Nicholas Matsumoto
  • Erik Gerdtsson
  • Amado Zurita
  • Christopher Logothetis
  • Paul G Corn
  • Ana M Aparicio
  • James Hicks
  • Peter Kuhn
Enheter & grupper
Externa organisationer
  • University of Southern California
  • University of Texas MD Anderson Cancer Center
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi
Originalspråkengelska
Artikelnummer1056
TidskriftCancers
Volym13
Utgåva nummer1056
StatusPublished - 2021 mar 12
PublikationskategoriForskning
Peer review utfördJa