Dysmetabolic circulating tumor cells are prognostic in metastatic breast cancer

Giulia Brisotto, Eva Biscontin, Elisabetta Rossi, Michela Bulfoni, Aigars Piruska, Simon Spazzapan, Cristina Poggiana, Riccardo Vidotto, Agostino Steffan, Alfonso Colombatti, Wilhelm T.S. Huck, Daniela Cesselli, Rita Zamarchi, Matteo Turetta, Fabio Del Ben

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number1005
Number of pages19
JournalCancers
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 2020

Keywords

  • Breast cancer
  • Circulating tumor cells
  • Droplet microfluidics
  • Liquid biopsy
  • Metabolism
  • PH

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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