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

Sandström Gerdtsson, Anna LU ; Setayesh, Sonia M ; Malihi, Paymaneh D ; Ruiz, Carmen ; Carlsson, Anders LU ; Rafael, Nevarez ; Matsumoto, Nicholas ; Gerdtsson, Erik ; Zurita, Amado and Logothetis, Christopher , et al. (2021) In Cancers 13(1056).
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancers
volume
13
issue
1056
article number
1056
publisher
MDPI AG
external identifiers
  • scopus:85101682876
  • pmid:33801459
ISSN
2072-6694
DOI
10.3390/cancers13051056
language
English
LU publication?
yes
id
58c29311-bdf9-42f1-be66-6c4c2099c0bc
date added to LUP
2021-03-18 22:50:23
date last changed
2022-04-27 00:53:52
@article{58c29311-bdf9-42f1-be66-6c4c2099c0bc,
  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.}},
  author       = {{Sandström Gerdtsson, Anna and Setayesh, Sonia M and Malihi, Paymaneh D and Ruiz, Carmen and Carlsson, Anders and Rafael, Nevarez and Matsumoto, Nicholas and Gerdtsson, Erik and Zurita, Amado and Logothetis, Christopher and Corn, Paul G and Aparicio, Ana M and Hicks, James and Kuhn, Peter}},
  issn         = {{2072-6694}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{1056}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Large Extracellular Vesicle Characterization and Association with Circulating Tumor Cells in Metastatic Castrate Resistant Prostate Cancer}},
  url          = {{http://dx.doi.org/10.3390/cancers13051056}},
  doi          = {{10.3390/cancers13051056}},
  volume       = {{13}},
  year         = {{2021}},
}