Dysmetabolic Circulating Tumor Cells Are Prognostic in Metastatic Breast Cancer
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 sin...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-04-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/4/1005 |
| _version_ | 1797570277943541760 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Giulia Brisotto |
| collection | DOAJ |
| description | 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; <i>p</i> < 0.0001) and during therapy (139 vs. 266 days; <i>p</i> = 0.0009); ii) a worse OS pre-therapy (<i>p</i> = 0.0003, 82% survival vs. 20%) and during therapy (<i>p</i> = 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. |
| first_indexed | 2024-03-10T20:22:39Z |
| format | Article |
| id | doaj.art-d4f33428ee94486784e28bc368d60d43 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T20:22:39Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d4f33428ee94486784e28bc368d60d432023-11-19T22:05:44ZengMDPI AGCancers2072-66942020-04-01124100510.3390/cancers12041005Dysmetabolic Circulating Tumor Cells Are Prognostic in Metastatic Breast CancerGiulia Brisotto0Eva Biscontin1Elisabetta Rossi2Michela Bulfoni3Aigars Piruska4Simon Spazzapan5Cristina Poggiana6Riccardo Vidotto7Agostino Steffan8Alfonso Colombatti9Wilhelm T. S. Huck10Daniela Cesselli11Rita Zamarchi12Matteo Turetta13Fabio Del Ben14Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyDepartment of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, ItalyDepartment of Pathology, ASUIUD University Hospital, 33100 Udine, ItalyInstitute for Molecules and Materials, Radboud University, 6525AJ Nijmegen, The NetherlandsDepartment of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyVeneto Institute of Oncology IOV-IRCCS, 35128 Padova, ItalyVeneto Institute of Oncology IOV-IRCCS, 35128 Padova, ItalyImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyInstitute for Molecules and Materials, Radboud University, 6525AJ Nijmegen, The NetherlandsDepartment of Medicine (DAME), University of Udine, 33100, ItalyVeneto Institute of Oncology IOV-IRCCS, 35128 Padova, ItalyImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyImmunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyCirculating 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; <i>p</i> < 0.0001) and during therapy (139 vs. 266 days; <i>p</i> = 0.0009); ii) a worse OS pre-therapy (<i>p</i> = 0.0003, 82% survival vs. 20%) and during therapy (<i>p</i> = 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.https://www.mdpi.com/2072-6694/12/4/1005breast cancercirculating tumor cellsliquid biopsymetabolismdroplet microfluidicspH |
| spellingShingle | 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 Dysmetabolic Circulating Tumor Cells Are Prognostic in Metastatic Breast Cancer Cancers breast cancer circulating tumor cells liquid biopsy metabolism droplet microfluidics pH |
| title | Dysmetabolic Circulating Tumor Cells Are Prognostic in Metastatic Breast Cancer |
| title_full | Dysmetabolic Circulating Tumor Cells Are Prognostic in Metastatic Breast Cancer |
| title_fullStr | Dysmetabolic Circulating Tumor Cells Are Prognostic in Metastatic Breast Cancer |
| title_full_unstemmed | Dysmetabolic Circulating Tumor Cells Are Prognostic in Metastatic Breast Cancer |
| title_short | Dysmetabolic Circulating Tumor Cells Are Prognostic in Metastatic Breast Cancer |
| title_sort | dysmetabolic circulating tumor cells are prognostic in metastatic breast cancer |
| topic | breast cancer circulating tumor cells liquid biopsy metabolism droplet microfluidics pH |
| url | https://www.mdpi.com/2072-6694/12/4/1005 |
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