TY - JOUR
T1 - Dysmetabolic circulating tumor cells are prognostic in metastatic breast cancer
AU - Brisotto, Giulia
AU - Biscontin, Eva
AU - Rossi, Elisabetta
AU - Bulfoni, Michela
AU - Piruska, Aigars
AU - Spazzapan, Simon
AU - Poggiana, Cristina
AU - Vidotto, Riccardo
AU - Steffan, Agostino
AU - Colombatti, Alfonso
AU - Huck, Wilhelm T.S.
AU - Cesselli, Daniela
AU - Zamarchi, Rita
AU - Turetta, Matteo
AU - Del Ben, Fabio
N1 - Funding Information:
Funding: This work was supported by CRO Aviano Intramural Research Grants-2014, ERC Monalisa QuidProQuo grant (Advanced Grant No. 269051), ERC “A Cactus” (poc Grant No.640955) proof of concept grant,AIRC IG “Dissecting the heterogeneity of circulating tumor cells in metastatic breast cancer: association with metastatic pattern and clinical outcome”, CUP: G23C17000800007 (ID 20443), Radboud University Proeftuin Nanomedicine grant. The TITAN X used for this research was donated by the NVIDIA Corporation.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4
Y1 - 2020/4
N2 - Circulating tumor cells (CTCs) belong to a heterogeneous pool of rare cells, and a unequivocal phenotypic definition of CTC is lacking. Here, we present a definition of metabolically-altered CTC (MBA-CTCs) as CD45-negative cells with an increased extracellular acidification rate, detected with a single-cell droplet microfluidic technique. We tested the prognostic value of MBA-CTCs in 31 metastatic breast cancer patients before starting a new systemic therapy (T0) and 3–4 weeks after (T1), comparing results with a parallel FDA-approved CellSearch (CS) approach. An increased level of MBA-CTCs was associated with: I) a shorter median PFS pre-therapy (123 days vs. 306; p < 0.0001) and during therapy (139 vs. 266 days; p = 0.0009); ii) a worse OS pre-therapy (p = 0.0003, 82% survival vs. 20%) and during therapy (p = 0.0301, 67% survival vs. 38%); iii) good agreement with therapy response (kappa = 0.685). The trend of MBA-CTCs over time (combining data at T0 and T1) added information with respect to separate evaluation of T0 and T1. The combined results of the two assays (MBA and CS) increased stratification accuracy, while correlation between MBA and CS was not significant, suggesting that the two assays are detecting different CTC subsets. In conclusion, this study suggests that MBA allows detection of both EpCAM-negative and EpCAM-positive, viable and label-free CTCs, which provide clinical information apparently equivalent and complementary to CS. A further validation of proposed method and cut-offs is needed in a larger, separate study.
AB - Circulating tumor cells (CTCs) belong to a heterogeneous pool of rare cells, and a unequivocal phenotypic definition of CTC is lacking. Here, we present a definition of metabolically-altered CTC (MBA-CTCs) as CD45-negative cells with an increased extracellular acidification rate, detected with a single-cell droplet microfluidic technique. We tested the prognostic value of MBA-CTCs in 31 metastatic breast cancer patients before starting a new systemic therapy (T0) and 3–4 weeks after (T1), comparing results with a parallel FDA-approved CellSearch (CS) approach. An increased level of MBA-CTCs was associated with: I) a shorter median PFS pre-therapy (123 days vs. 306; p < 0.0001) and during therapy (139 vs. 266 days; p = 0.0009); ii) a worse OS pre-therapy (p = 0.0003, 82% survival vs. 20%) and during therapy (p = 0.0301, 67% survival vs. 38%); iii) good agreement with therapy response (kappa = 0.685). The trend of MBA-CTCs over time (combining data at T0 and T1) added information with respect to separate evaluation of T0 and T1. The combined results of the two assays (MBA and CS) increased stratification accuracy, while correlation between MBA and CS was not significant, suggesting that the two assays are detecting different CTC subsets. In conclusion, this study suggests that MBA allows detection of both EpCAM-negative and EpCAM-positive, viable and label-free CTCs, which provide clinical information apparently equivalent and complementary to CS. A further validation of proposed method and cut-offs is needed in a larger, separate study.
KW - Breast cancer
KW - Circulating tumor cells
KW - Droplet microfluidics
KW - Liquid biopsy
KW - Metabolism
KW - PH
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U2 - 10.3390/cancers12041005
DO - 10.3390/cancers12041005
M3 - Article
AN - SCOPUS:85084004531
VL - 12
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 4
M1 - 1005
ER -