Longitudinal CTCs gene expression analysis on metastatic castration-resistant prostate cancer patients treated with docetaxel reveals new potential prognosis markers

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 -