Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients

Afroditi Nanou; Frank A.W. Coumans; Guus van Dalum; Leonie L. Zeune; David Dolling; Wendy Onstenk; Mateus Crespo; Mariane Sousa Fontes; Pasquale Rescigno; Gemma Fowler; Penny Flohr; Christoph Brune; Stefan Sleijfer; Johann S. de Bono; Leon W.M.M. Terstappen

doi:10.18632/oncotarget.25019

Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients

Afroditi Nanou^* (Corresponding Author)
, Frank A.W. Coumans
, Guus van Dalum
, Leonie L. Zeune
, David Dolling
, Wendy Onstenk
, Mateus Crespo
, Mariane Sousa Fontes
, Pasquale Rescigno
, Gemma Fowler
, Penny Flohr
, Christoph Brune
, Stefan Sleijfer
, Johann S. de Bono
, Leon W.M.M. Terstappen

^*Corresponding author for this work

Medical Cell Biophysics

Research output: Contribution to journal › Article › Academic › peer-review

66 Citations (Scopus)

202 Downloads (Pure)

Abstract

Purpose: The presence of Circulating Tumor Cells (CTCs) in Castration-Resistant Prostate Cancer (CRPC) patients is associated with poor prognosis. In this study, we evaluated the association of clinical outcome in 129 CRPC patients with CTCs, tumor-derived Extracellular Vesicles (tdEVs) and plasma levels of total (CK18) and caspase-cleaved cytokeratin 18 (ccCK18).

Experimental Design: CTCs and tdEVs were isolated with the CellSearch system and automatically enumerated. Cut-off values dichotomizing patients into favorable and unfavorable groups of overall survival were set on a retrospective data set of 84 patients and validated on a prospective data set of 45 patients. Plasma levels of CK18 and ccCK18 were assessed by ELISAs.

Results: CTCs, tdEVs and both cytokeratin plasma levels were significantly increased in CRPC patients compared to healthy donors (HDs). All biomarkers except for ccCK18 were prognostic showing a decreased median overall survival for the unfavorable groups of 9.2 vs 21.1, 8.1 vs 23.0 and 10.0 vs 21.5 months respectively. In multivariable Cox regression analysis, tdEVs remained significant.

Conclusions: Automated CTC and tdEV enumeration allows fast and reliable scoring eliminating inter- and intra- operator variability. tdEVs provide similar prognostic information to CTC counts.

Original language	English
Pages (from-to)	19283-19293
Number of pages	11
Journal	Oncotarget
Volume	9
Issue number	27
DOIs	https://doi.org/10.18632/oncotarget.25019
Publication status	Published - 10 Apr 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Castration-resistant prostate cancer (CRPC)
Circulating tumor cells (CTCs)
Cytokeratin 18 (CK18)
Tumor-derived Extracellular Vesicles (tdEVs)
Caspase-cleaved cytokeratin 18 (ccCK18)

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Nanou2018circulatingFinal published version, 2.12 MBLicence: CC BY

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Nanou, A., Coumans, F. A. W., Dalum, G. V., Zeune, L. L., Dolling, D., Onstenk, W., Crespo, M., Fontes, M. S., Rescigno, P., Fowler, G., Flohr, P., Brune, C., Sleijfer, S., de Bono, J. S., & Terstappen, L. W. M. M. (2018). Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients. Oncotarget, 9(27), 19283-19293. https://doi.org/10.18632/oncotarget.25019

@article{b66498531c4a4fab8f42e76c5c1a8e69,

title = "Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients",

abstract = "Purpose: The presence of Circulating Tumor Cells (CTCs) in Castration-Resistant Prostate Cancer (CRPC) patients is associated with poor prognosis. In this study, we evaluated the association of clinical outcome in 129 CRPC patients with CTCs, tumor-derived Extracellular Vesicles (tdEVs) and plasma levels of total (CK18) and caspase-cleaved cytokeratin 18 (ccCK18). Experimental Design: CTCs and tdEVs were isolated with the CellSearch system and automatically enumerated. Cut-off values dichotomizing patients into favorable and unfavorable groups of overall survival were set on a retrospective data set of 84 patients and validated on a prospective data set of 45 patients. Plasma levels of CK18 and ccCK18 were assessed by ELISAs. Results: CTCs, tdEVs and both cytokeratin plasma levels were significantly increased in CRPC patients compared to healthy donors (HDs). All biomarkers except for ccCK18 were prognostic showing a decreased median overall survival for the unfavorable groups of 9.2 vs 21.1, 8.1 vs 23.0 and 10.0 vs 21.5 months respectively. In multivariable Cox regression analysis, tdEVs remained significant.Conclusions: Automated CTC and tdEV enumeration allows fast and reliable scoring eliminating inter- and intra- operator variability. tdEVs provide similar prognostic information to CTC counts.",

keywords = "Castration-resistant prostate cancer (CRPC), Circulating tumor cells (CTCs), Cytokeratin 18 (CK18), Tumor-derived Extracellular Vesicles (tdEVs), Caspase-cleaved cytokeratin 18 (ccCK18)",

author = "Afroditi Nanou and Coumans, \{Frank A.W.\} and Dalum, \{Guus van\} and Zeune, \{Leonie L.\} and David Dolling and Wendy Onstenk and Mateus Crespo and Fontes, \{Mariane Sousa\} and Pasquale Rescigno and Gemma Fowler and Penny Flohr and Christoph Brune and Stefan Sleijfer and \{de Bono\}, \{Johann S.\} and Terstappen, \{Leon W.M.M.\}",

year = "2018",

month = apr,

day = "10",

doi = "10.18632/oncotarget.25019",

language = "English",

volume = "9",

pages = "19283--19293",

journal = "Oncotarget",

issn = "1949-2553",

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number = "27",

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Nanou, A, Coumans, FAW, Dalum, GV, Zeune, LL, Dolling, D, Onstenk, W, Crespo, M, Fontes, MS, Rescigno, P, Fowler, G, Flohr, P, Brune, C, Sleijfer, S, de Bono, JS & Terstappen, LWMM 2018, 'Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients', Oncotarget, vol. 9, no. 27, pp. 19283-19293. https://doi.org/10.18632/oncotarget.25019

TY - JOUR

T1 - Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients

AU - Nanou, Afroditi

AU - Coumans, Frank A.W.

AU - Dalum, Guus van

AU - Zeune, Leonie L.

AU - Dolling, David

AU - Onstenk, Wendy

AU - Crespo, Mateus

AU - Fontes, Mariane Sousa

AU - Rescigno, Pasquale

AU - Fowler, Gemma

AU - Flohr, Penny

AU - Brune, Christoph

AU - Sleijfer, Stefan

AU - de Bono, Johann S.

AU - Terstappen, Leon W.M.M.

PY - 2018/4/10

Y1 - 2018/4/10

N2 - Purpose: The presence of Circulating Tumor Cells (CTCs) in Castration-Resistant Prostate Cancer (CRPC) patients is associated with poor prognosis. In this study, we evaluated the association of clinical outcome in 129 CRPC patients with CTCs, tumor-derived Extracellular Vesicles (tdEVs) and plasma levels of total (CK18) and caspase-cleaved cytokeratin 18 (ccCK18). Experimental Design: CTCs and tdEVs were isolated with the CellSearch system and automatically enumerated. Cut-off values dichotomizing patients into favorable and unfavorable groups of overall survival were set on a retrospective data set of 84 patients and validated on a prospective data set of 45 patients. Plasma levels of CK18 and ccCK18 were assessed by ELISAs. Results: CTCs, tdEVs and both cytokeratin plasma levels were significantly increased in CRPC patients compared to healthy donors (HDs). All biomarkers except for ccCK18 were prognostic showing a decreased median overall survival for the unfavorable groups of 9.2 vs 21.1, 8.1 vs 23.0 and 10.0 vs 21.5 months respectively. In multivariable Cox regression analysis, tdEVs remained significant.Conclusions: Automated CTC and tdEV enumeration allows fast and reliable scoring eliminating inter- and intra- operator variability. tdEVs provide similar prognostic information to CTC counts.

AB - Purpose: The presence of Circulating Tumor Cells (CTCs) in Castration-Resistant Prostate Cancer (CRPC) patients is associated with poor prognosis. In this study, we evaluated the association of clinical outcome in 129 CRPC patients with CTCs, tumor-derived Extracellular Vesicles (tdEVs) and plasma levels of total (CK18) and caspase-cleaved cytokeratin 18 (ccCK18). Experimental Design: CTCs and tdEVs were isolated with the CellSearch system and automatically enumerated. Cut-off values dichotomizing patients into favorable and unfavorable groups of overall survival were set on a retrospective data set of 84 patients and validated on a prospective data set of 45 patients. Plasma levels of CK18 and ccCK18 were assessed by ELISAs. Results: CTCs, tdEVs and both cytokeratin plasma levels were significantly increased in CRPC patients compared to healthy donors (HDs). All biomarkers except for ccCK18 were prognostic showing a decreased median overall survival for the unfavorable groups of 9.2 vs 21.1, 8.1 vs 23.0 and 10.0 vs 21.5 months respectively. In multivariable Cox regression analysis, tdEVs remained significant.Conclusions: Automated CTC and tdEV enumeration allows fast and reliable scoring eliminating inter- and intra- operator variability. tdEVs provide similar prognostic information to CTC counts.

KW - Castration-resistant prostate cancer (CRPC)

KW - Circulating tumor cells (CTCs)

KW - Cytokeratin 18 (CK18)

KW - Tumor-derived Extracellular Vesicles (tdEVs)

KW - Caspase-cleaved cytokeratin 18 (ccCK18)

UR - https://www.scopus.com/pages/publications/85045217628

U2 - 10.18632/oncotarget.25019

DO - 10.18632/oncotarget.25019

M3 - Article

AN - SCOPUS:85045217628

SN - 1949-2553

VL - 9

SP - 19283

EP - 19293

JO - Oncotarget

JF - Oncotarget

IS - 27

ER -

Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients

Abstract

UN SDGs

Keywords

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