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 - http://www.scopus.com/inward/record.url?scp=85045217628&partnerID=8YFLogxK
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 -
