Longitudinal CTCs gene expression analysis on metastatic castration-resistant prostate cancer patients treated with docetaxel reveals new potential prognosis markers
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Longitudinal CTCs gene expression analysis on metastatic castration-resistant prostate cancer patients treated with docetaxel reveals new potential prognosis markers. / Pereira-Veiga, Thais; González-Conde, Miriam; León-Mateos, Luis; Piñeiro-Cid, Roberto; Abuín, Carmen; Muinelo-Romay, Laura; Martínez-Fernández, Mónica; Brea Iglesias, Jenifer; García González, Jorge; Anido, Urbano; Aguín-Losada, Santiago; Cebey, Víctor; Costa, Clotilde; López-López, Rafael.
in: CLIN EXP METASTAS, Jahrgang 38, Nr. 2, 04.2021, S. 239-251.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Longitudinal CTCs gene expression analysis on metastatic castration-resistant prostate cancer patients treated with docetaxel reveals new potential prognosis markers
AU - Pereira-Veiga, Thais
AU - González-Conde, Miriam
AU - León-Mateos, Luis
AU - Piñeiro-Cid, Roberto
AU - Abuín, Carmen
AU - Muinelo-Romay, Laura
AU - Martínez-Fernández, Mónica
AU - Brea Iglesias, Jenifer
AU - García González, Jorge
AU - Anido, Urbano
AU - Aguín-Losada, Santiago
AU - Cebey, Víctor
AU - Costa, Clotilde
AU - López-López, Rafael
PY - 2021/4
Y1 - 2021/4
N2 - CTCs have extensively been used for the monitoring and characterization of metastatic prostate cancer, but their application in the clinic is still very scarce. Besides, the resistance mechanisms linked to prostate cancer treatment remain unclear. Liquid biopsies represent the most promising alternative due to the complexity of biopsying bone metastasis and the duration of the disease. We performed a prospective longitudinal study in CTCs from 20 castration-resistant prostate cancer patients treated with docetaxel. For that, we used CellSearch® technology and a custom gene expression panel with qRT-PCR using a CTCs negative enrichment approach. We found that CTCs showed a hybrid phenotype during the disease, where epithelial features were associated with the presence of ≥ 5 CTCs/7.5 mL of blood, while high relative expression of the gene MYCL was observed preferentially in the set of samples with < 5 CTCs/7.5 mL of blood. At baseline, patients whose CTCs had stem or hybrid features showed a later progression. After 1 cycle of docetaxel, high relative expression of ZEB1 indicated worse outcome, while KRT19 and KLK3 high expression could predisposed the patients to a worse prognosis at clinical progression. In the present work we describe biomarkers with clinical relevance for the prediction of early response or resistance in castration-resistant prostate cancer patients. Besides, we question the utility of targeted isolated CTCs and the use of a limited number of markers to define the CTCs population.
AB - CTCs have extensively been used for the monitoring and characterization of metastatic prostate cancer, but their application in the clinic is still very scarce. Besides, the resistance mechanisms linked to prostate cancer treatment remain unclear. Liquid biopsies represent the most promising alternative due to the complexity of biopsying bone metastasis and the duration of the disease. We performed a prospective longitudinal study in CTCs from 20 castration-resistant prostate cancer patients treated with docetaxel. For that, we used CellSearch® technology and a custom gene expression panel with qRT-PCR using a CTCs negative enrichment approach. We found that CTCs showed a hybrid phenotype during the disease, where epithelial features were associated with the presence of ≥ 5 CTCs/7.5 mL of blood, while high relative expression of the gene MYCL was observed preferentially in the set of samples with < 5 CTCs/7.5 mL of blood. At baseline, patients whose CTCs had stem or hybrid features showed a later progression. After 1 cycle of docetaxel, high relative expression of ZEB1 indicated worse outcome, while KRT19 and KLK3 high expression could predisposed the patients to a worse prognosis at clinical progression. In the present work we describe biomarkers with clinical relevance for the prediction of early response or resistance in castration-resistant prostate cancer patients. Besides, we question the utility of targeted isolated CTCs and the use of a limited number of markers to define the CTCs population.
KW - Aged
KW - Aged, 80 and over
KW - Cell Count
KW - Docetaxel/therapeutic use
KW - Epithelial-Mesenchymal Transition
KW - Humans
KW - Male
KW - Middle Aged
KW - Neoplastic Cells, Circulating/metabolism
KW - Prognosis
KW - Prostatic Neoplasms, Castration-Resistant/drug therapy
KW - Proto-Oncogene Proteins c-myc/genetics
KW - Transcriptome
KW - Zinc Finger E-box-Binding Homeobox 1/genetics
U2 - 10.1007/s10585-021-10075-1
DO - 10.1007/s10585-021-10075-1
M3 - SCORING: Journal article
C2 - 33635497
VL - 38
SP - 239
EP - 251
JO - CLIN EXP METASTAS
JF - CLIN EXP METASTAS
SN - 0262-0898
IS - 2
ER -