Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients.
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Embargo End Date
ICR Authors
Authors
Nanou, A
Coumans, FAW
van Dalum, G
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
Coumans, FAW
van Dalum, G
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
Document Type
Journal Article
Date
2018-04-10
Date Accepted
2018-03-17
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.
Citation
Oncotarget, 2018, 9 (27), pp. 19283 - 19293
Source Title
Publisher
Impact Journals, LLC
ISSN
1949-2553
eISSN
1949-2553
Collections
Research Team
Cancer Biomarkers
Prostate Cancer Targeted Therapy Group
Prostate Cancer Targeted Therapy Group