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A Pilot Study of the Predictive Potential of Chemosensitivity and Gene Expression Assays Using Circulating Tumour Cells from Patients with Recurrent Ovarian Cancer

Circulating tumour cells (CTCs) from liquid biopsies are under current investigation in several cancers, including epithelial ovarian cancer (EOC) but face significant drawbacks in terms of non-standardised methodology, low viable cell numbers and accuracy of CTC identification. In this pilot study,...

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Autores principales: Guadagni, Stefano, Clementi, Marco, Masedu, Francesco, Fiorentini, Giammaria, Sarti, Donatella, Deraco, Marcello, Kusamura, Shigeki, Papasotiriou, Ioannis, Apostolou, Panagiotis, Aigner, Karl Reinhard, Zavattieri, Giuseppe, Farina, Antonietta Rossella, Vizzielli, Giuseppe, Scambia, Giovanni, Mackay, Andrew Reay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370156/
https://www.ncbi.nlm.nih.gov/pubmed/32646060
http://dx.doi.org/10.3390/ijms21134813
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author Guadagni, Stefano
Clementi, Marco
Masedu, Francesco
Fiorentini, Giammaria
Sarti, Donatella
Deraco, Marcello
Kusamura, Shigeki
Papasotiriou, Ioannis
Apostolou, Panagiotis
Aigner, Karl Reinhard
Zavattieri, Giuseppe
Farina, Antonietta Rossella
Vizzielli, Giuseppe
Scambia, Giovanni
Mackay, Andrew Reay
author_facet Guadagni, Stefano
Clementi, Marco
Masedu, Francesco
Fiorentini, Giammaria
Sarti, Donatella
Deraco, Marcello
Kusamura, Shigeki
Papasotiriou, Ioannis
Apostolou, Panagiotis
Aigner, Karl Reinhard
Zavattieri, Giuseppe
Farina, Antonietta Rossella
Vizzielli, Giuseppe
Scambia, Giovanni
Mackay, Andrew Reay
author_sort Guadagni, Stefano
collection PubMed
description Circulating tumour cells (CTCs) from liquid biopsies are under current investigation in several cancers, including epithelial ovarian cancer (EOC) but face significant drawbacks in terms of non-standardised methodology, low viable cell numbers and accuracy of CTC identification. In this pilot study, we report that chemosensitivity assays using liquid biopsy-derived metastatic EOC CTCs, from 10 patients, nine with stage IIIC and one with stage IV disease, in progression after systemic chemotherapy, submitted for hypoxic isolated abdominal perfusion (HAP), are both feasible and useful in predicting response to therapy. Viable metastatic EOC CTCs (>5 cells/mL for all 10 blood samples), enriched by transient culture and identified by reverse transcription polymerase chain reaction (RT-PCR) and indirect immunofluorescence (IF), were subjected to flow cytometry-based Annexin V-PE assays for chemosensitivity to several chemotherapeutic agents and by RT-PCR for tumour gene expression profiling. Using a cut-off value of >80% cell death, CTC chemosensitivity tests were predictive of patient RECIST 1.1 responses to HAP therapy associated with 100% sensitivity, 50% specificity, 33% positive predictive, 100% negative predictive and 60% accuracy values. We propose that the methodology employed in this study is feasible and has the potential to predict response to therapy, setting the stage for a larger study.
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spelling pubmed-73701562020-07-21 A Pilot Study of the Predictive Potential of Chemosensitivity and Gene Expression Assays Using Circulating Tumour Cells from Patients with Recurrent Ovarian Cancer Guadagni, Stefano Clementi, Marco Masedu, Francesco Fiorentini, Giammaria Sarti, Donatella Deraco, Marcello Kusamura, Shigeki Papasotiriou, Ioannis Apostolou, Panagiotis Aigner, Karl Reinhard Zavattieri, Giuseppe Farina, Antonietta Rossella Vizzielli, Giuseppe Scambia, Giovanni Mackay, Andrew Reay Int J Mol Sci Article Circulating tumour cells (CTCs) from liquid biopsies are under current investigation in several cancers, including epithelial ovarian cancer (EOC) but face significant drawbacks in terms of non-standardised methodology, low viable cell numbers and accuracy of CTC identification. In this pilot study, we report that chemosensitivity assays using liquid biopsy-derived metastatic EOC CTCs, from 10 patients, nine with stage IIIC and one with stage IV disease, in progression after systemic chemotherapy, submitted for hypoxic isolated abdominal perfusion (HAP), are both feasible and useful in predicting response to therapy. Viable metastatic EOC CTCs (>5 cells/mL for all 10 blood samples), enriched by transient culture and identified by reverse transcription polymerase chain reaction (RT-PCR) and indirect immunofluorescence (IF), were subjected to flow cytometry-based Annexin V-PE assays for chemosensitivity to several chemotherapeutic agents and by RT-PCR for tumour gene expression profiling. Using a cut-off value of >80% cell death, CTC chemosensitivity tests were predictive of patient RECIST 1.1 responses to HAP therapy associated with 100% sensitivity, 50% specificity, 33% positive predictive, 100% negative predictive and 60% accuracy values. We propose that the methodology employed in this study is feasible and has the potential to predict response to therapy, setting the stage for a larger study. MDPI 2020-07-07 /pmc/articles/PMC7370156/ /pubmed/32646060 http://dx.doi.org/10.3390/ijms21134813 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guadagni, Stefano
Clementi, Marco
Masedu, Francesco
Fiorentini, Giammaria
Sarti, Donatella
Deraco, Marcello
Kusamura, Shigeki
Papasotiriou, Ioannis
Apostolou, Panagiotis
Aigner, Karl Reinhard
Zavattieri, Giuseppe
Farina, Antonietta Rossella
Vizzielli, Giuseppe
Scambia, Giovanni
Mackay, Andrew Reay
A Pilot Study of the Predictive Potential of Chemosensitivity and Gene Expression Assays Using Circulating Tumour Cells from Patients with Recurrent Ovarian Cancer
title A Pilot Study of the Predictive Potential of Chemosensitivity and Gene Expression Assays Using Circulating Tumour Cells from Patients with Recurrent Ovarian Cancer
title_full A Pilot Study of the Predictive Potential of Chemosensitivity and Gene Expression Assays Using Circulating Tumour Cells from Patients with Recurrent Ovarian Cancer
title_fullStr A Pilot Study of the Predictive Potential of Chemosensitivity and Gene Expression Assays Using Circulating Tumour Cells from Patients with Recurrent Ovarian Cancer
title_full_unstemmed A Pilot Study of the Predictive Potential of Chemosensitivity and Gene Expression Assays Using Circulating Tumour Cells from Patients with Recurrent Ovarian Cancer
title_short A Pilot Study of the Predictive Potential of Chemosensitivity and Gene Expression Assays Using Circulating Tumour Cells from Patients with Recurrent Ovarian Cancer
title_sort pilot study of the predictive potential of chemosensitivity and gene expression assays using circulating tumour cells from patients with recurrent ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370156/
https://www.ncbi.nlm.nih.gov/pubmed/32646060
http://dx.doi.org/10.3390/ijms21134813
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