A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNA
BackgroundThymic epithelial tumors (TETs) are rare thoracic malignancies, commonly divided into two different histopathological entities, thymoma (T) and thymic carcinoma (TC). To date, there are no specific biomarkers for monitoring the biological course of these rare tumors. We carried out a singl...
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2021-02-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.602153/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Margaret Ottaviano Margaret Ottaviano Margaret Ottaviano Mario Giuliano Mario Giuliano Marianna Tortora Marianna Tortora Evelina La Civita Antonietta Liotti Michele Longo Dario Bruzzese Michele Cennamo Vittorio Riccio Pietro De Placido Fernanda Picozzi Sara Parola Bruno Daniele Gerardo Botti Gerardo Botti Pietro Formisano Francesco Beguinot Sabino De Placido Sabino De Placido Daniela Terracciano Giovannella Palmieri |
spellingShingle |
Margaret Ottaviano Margaret Ottaviano Margaret Ottaviano Mario Giuliano Mario Giuliano Marianna Tortora Marianna Tortora Evelina La Civita Antonietta Liotti Michele Longo Dario Bruzzese Michele Cennamo Vittorio Riccio Pietro De Placido Fernanda Picozzi Sara Parola Bruno Daniele Gerardo Botti Gerardo Botti Pietro Formisano Francesco Beguinot Sabino De Placido Sabino De Placido Daniela Terracciano Giovannella Palmieri A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNA Frontiers in Oncology thymic epithelial tumors circulating cell-free DNA biomarkers stage system circulating tumor DNA thymoma |
author_facet |
Margaret Ottaviano Margaret Ottaviano Margaret Ottaviano Mario Giuliano Mario Giuliano Marianna Tortora Marianna Tortora Evelina La Civita Antonietta Liotti Michele Longo Dario Bruzzese Michele Cennamo Vittorio Riccio Pietro De Placido Fernanda Picozzi Sara Parola Bruno Daniele Gerardo Botti Gerardo Botti Pietro Formisano Francesco Beguinot Sabino De Placido Sabino De Placido Daniela Terracciano Giovannella Palmieri |
author_sort |
Margaret Ottaviano |
title |
A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNA |
title_short |
A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNA |
title_full |
A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNA |
title_fullStr |
A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNA |
title_full_unstemmed |
A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNA |
title_sort |
new horizon of liquid biopsy in thymic epithelial tumors: the potential utility of circulating cell-free dna |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-02-01 |
description |
BackgroundThymic epithelial tumors (TETs) are rare thoracic malignancies, commonly divided into two different histopathological entities, thymoma (T) and thymic carcinoma (TC). To date, there are no specific biomarkers for monitoring the biological course of these rare tumors. We carried out a single center study aiming at the detection of circulating cell-free DNA (ccfDNA) and the correlation of its levels with metastatic dissemination and histological subtype in patients with TETs.MethodsFrom July 2018 to January 2020, 5-ml blood samples from 26 patients with advanced TET (aTET) (11 patients with TC and 15 patients with T) and from six patients with completely resected TET (cr-TET), were prospectively obtained before the initiation of systemic therapy. Blood samples from 10 healthy donors were used as control. The QIAamp MinElute ccfDNA Kits was used for ccfDNA isolation from plasma; real-time PCR was used for cfDNA quantification.ResultsWe found significantly higher ccfDNA amount in patients with T and TC compared to controls, with median ccfDNA level of 3.3 ng/µl, 11.4 ng/µl and 25.6 ng/µl, for healthy donors, T and TC patients, respectively (p<0.001). No significant difference was found between cr-TET and controls (p = 0.175). ccfDNA concentrations were higher in metastatic (M1a and M1b) compared to non-metastatic (M0) TETs (25.6 ng/µl versus 7.2 ng/µl; p= 0.037). No significant correlation was found either between ccfDNA and disease stage, according to both the Masaoka-Koga (p= 0.854) and the TNM 8th edition staging systems (p = 0.66), or between ccfDNA levels and overall tumor burden, estimated according RECIST 1.1 criteria (r = 0.07, p = 0.725).ConclusionsTo the best of our knowledge, this is the first study that prospectively explores detection and quantification of ccfDNA in TETs. Higher baseline cfDNA levels have been observed in both advanced T and TC comparing to the control group. |
topic |
thymic epithelial tumors circulating cell-free DNA biomarkers stage system circulating tumor DNA thymoma |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2020.602153/full |
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doaj-41b37b8d68384d7f9cb966ddb79785532021-02-04T06:02:39ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-02-011010.3389/fonc.2020.602153602153A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNAMargaret Ottaviano0Margaret Ottaviano1Margaret Ottaviano2Mario Giuliano3Mario Giuliano4Marianna Tortora5Marianna Tortora6Evelina La Civita7Antonietta Liotti8Michele Longo9Dario Bruzzese10Michele Cennamo11Vittorio Riccio12Pietro De Placido13Fernanda Picozzi14Sara Parola15Bruno Daniele16Gerardo Botti17Gerardo Botti18Pietro Formisano19Francesco Beguinot20Sabino De Placido21Sabino De Placido22Daniela Terracciano23Giovannella Palmieri24Department of Clinical Medicine and Surgery, Università degli Studi di Napoli “Federico II”, Naples, ItalyCRCTR Rare Tumors Coordinating Center of Campania Region, Naples, ItalyOncology Unit, Ospedale del Mare, Naples, ItalyDepartment of Clinical Medicine and Surgery, Università degli Studi di Napoli “Federico II”, Naples, ItalyCRCTR Rare Tumors Coordinating Center of Campania Region, Naples, ItalyCRCTR Rare Tumors Coordinating Center of Campania Region, Naples, ItalyDepartment of Translational Medical Sciences, Università degli Studi di Napoli “Federico II”, Naples, ItalyDepartment of Translational Medical Sciences, Università degli Studi di Napoli “Federico II”, Naples, ItalyDepartment of Translational Medical Sciences, Università degli Studi di Napoli “Federico II”, Naples, ItalyDepartment of Translational Medical Sciences, Università degli Studi di Napoli “Federico II”, Naples, ItalyDepartment of Public Health, Università degli Studi di Napoli “Federico II”, Naples, ItalyDepartment of Translational Medical Sciences, Università degli Studi di Napoli “Federico II”, Naples, ItalyDepartment of Clinical Medicine and Surgery, Università degli Studi di Napoli “Federico II”, Naples, ItalyDepartment of Clinical Medicine and Surgery, Università degli Studi di Napoli “Federico II”, Naples, ItalyDepartment of Clinical Medicine and Surgery, Università degli Studi di Napoli “Federico II”, Naples, ItalyDepartment of Clinical Medicine and Surgery, Università degli Studi di Napoli “Federico II”, Naples, ItalyOncology Unit, Ospedale del Mare, Naples, ItalyCRCTR Rare Tumors Coordinating Center of Campania Region, Naples, ItalyPathology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, ItalyDepartment of Translational Medical Sciences, Università degli Studi di Napoli “Federico II”, Naples, ItalyDepartment of Translational Medical Sciences, Università degli Studi di Napoli “Federico II”, Naples, ItalyDepartment of Clinical Medicine and Surgery, Università degli Studi di Napoli “Federico II”, Naples, ItalyCRCTR Rare Tumors Coordinating Center of Campania Region, Naples, ItalyDepartment of Translational Medical Sciences, Università degli Studi di Napoli “Federico II”, Naples, ItalyCRCTR Rare Tumors Coordinating Center of Campania Region, Naples, ItalyBackgroundThymic epithelial tumors (TETs) are rare thoracic malignancies, commonly divided into two different histopathological entities, thymoma (T) and thymic carcinoma (TC). To date, there are no specific biomarkers for monitoring the biological course of these rare tumors. We carried out a single center study aiming at the detection of circulating cell-free DNA (ccfDNA) and the correlation of its levels with metastatic dissemination and histological subtype in patients with TETs.MethodsFrom July 2018 to January 2020, 5-ml blood samples from 26 patients with advanced TET (aTET) (11 patients with TC and 15 patients with T) and from six patients with completely resected TET (cr-TET), were prospectively obtained before the initiation of systemic therapy. Blood samples from 10 healthy donors were used as control. The QIAamp MinElute ccfDNA Kits was used for ccfDNA isolation from plasma; real-time PCR was used for cfDNA quantification.ResultsWe found significantly higher ccfDNA amount in patients with T and TC compared to controls, with median ccfDNA level of 3.3 ng/µl, 11.4 ng/µl and 25.6 ng/µl, for healthy donors, T and TC patients, respectively (p<0.001). No significant difference was found between cr-TET and controls (p = 0.175). ccfDNA concentrations were higher in metastatic (M1a and M1b) compared to non-metastatic (M0) TETs (25.6 ng/µl versus 7.2 ng/µl; p= 0.037). No significant correlation was found either between ccfDNA and disease stage, according to both the Masaoka-Koga (p= 0.854) and the TNM 8th edition staging systems (p = 0.66), or between ccfDNA levels and overall tumor burden, estimated according RECIST 1.1 criteria (r = 0.07, p = 0.725).ConclusionsTo the best of our knowledge, this is the first study that prospectively explores detection and quantification of ccfDNA in TETs. Higher baseline cfDNA levels have been observed in both advanced T and TC comparing to the control group.https://www.frontiersin.org/articles/10.3389/fonc.2020.602153/fullthymic epithelial tumorscirculating cell-free DNAbiomarkersstage systemcirculating tumor DNAthymoma |