A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNA.
biomarkers
circulating cell-free DNA
circulating tumor DNA
stage system
thymic carcinoma
thymic epithelial tumors
thymoma
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2020
2020
Historique:
received:
02
09
2020
accepted:
02
12
2020
entrez:
26
2
2021
pubmed:
27
2
2021
medline:
27
2
2021
Statut:
epublish
Résumé
Thymic 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. From 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. We 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). To 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.
Sections du résumé
BACKGROUND
BACKGROUND
Thymic 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.
METHODS
METHODS
From 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.
RESULTS
RESULTS
We 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).
CONCLUSIONS
CONCLUSIONS
To 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.
Identifiants
pubmed: 33634024
doi: 10.3389/fonc.2020.602153
pmc: PMC7902074
doi:
Types de publication
Journal Article
Langues
eng
Pagination
602153Informations de copyright
Copyright © 2021 Ottaviano, Giuliano, Tortora, La Civita, Liotti, Longo, Bruzzese, Cennamo, Riccio, De Placido, Picozzi, Parola, Daniele, Botti, Formisano, Beguinot, De Placido, Terracciano and Palmieri.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Transl Lung Cancer Res. 2017 Dec;6(6):648-660
pubmed: 29218268
BMC Cancer. 2020 Feb 5;20(1):99
pubmed: 32024476
Rev Med Interne. 2018 Jan;39(1):17-26
pubmed: 28365191
Oncotarget. 2018 Jan 19;9(12):10549-10560
pubmed: 29535826
Cancer Treat Rev. 2018 Dec;71:76-87
pubmed: 30366202
J Thorac Oncol. 2014 Sep;9(9 Suppl 2):S73-80
pubmed: 25396315
Oncotarget. 2016 Jul 26;7(30):48832-48841
pubmed: 27223063
Pathol Int. 1994 May;44(5):359-67
pubmed: 8044305
Lung Cancer. 2016 Jun;96:48-51
pubmed: 27133749
Cancer Invest. 2019;37(9):432-439
pubmed: 31516038
Am Soc Clin Oncol Educ Book. 2019 Jan;39:543-552
pubmed: 31099677
Cancer Genet. 2018 Dec;228-229:159-168
pubmed: 29572011
Anal Biochem. 2018 Feb 1;542:34-39
pubmed: 29137972
BMC Med. 2018 Oct 2;16(1):166
pubmed: 30285732
Am J Surg Pathol. 2015 Apr;39(4):427-41
pubmed: 25634747
PLoS One. 2017 Feb 10;12(2):e0171991
pubmed: 28187169
Cancer Treat Rev. 2020 Jun;86:102014
pubmed: 32272379
J Thorac Oncol. 2010 Oct;5(10 Suppl 4):S266-72
pubmed: 20859117
J Thorac Dis. 2014 May;6 Suppl 2:S228-37
pubmed: 24868441
Int J Cancer. 2019 Aug 15;145(4):1148-1161
pubmed: 30779112
J Clin Oncol. 2011 Dec 20;29(36):4820-7
pubmed: 22105817
J Mater Chem B. 2019 Nov 21;7(43):6670-6704
pubmed: 31646316
Recent Results Cancer Res. 2020;215:231-252
pubmed: 31605232
Cancer Cell. 2018 Feb 12;33(2):244-258.e10
pubmed: 29438696
Annu Rev Med. 2012;63:199-215
pubmed: 22053740
Curr Opin Oncol. 2017 Jan;29(1):73-78
pubmed: 27906860
J Thorac Oncol. 2014 Sep;9(9 Suppl 2):S65-72
pubmed: 25396314
N Engl J Med. 2018 Nov 01;379(18):1754-1765
pubmed: 30380390
Semin Cancer Biol. 2018 Oct;52(Pt 1):56-73
pubmed: 28882552
Lung Cancer. 2014 Feb;83(2):126-32
pubmed: 24377980
Ann Oncol. 2015 Sep;26 Suppl 5:v40-55
pubmed: 26314779
J Thorac Oncol. 2014 May;9(5):596-611
pubmed: 24722150
Mol Oncol. 2016 Mar;10(3):464-74
pubmed: 26776681
Mol Diagn Ther. 2014 Jun;18(3):273-84
pubmed: 24385403
J Thorac Oncol. 2014 Sep;9(9 Suppl 2):S81-7
pubmed: 25396316
Cancer Genet. 2017 Dec;218-219:39-50
pubmed: 29153095
Micromachines (Basel). 2018 Feb 28;9(3):
pubmed: 30424034
Cancer. 1981 Dec 1;48(11):2485-92
pubmed: 7296496
J Thorac Oncol. 2015 Sep;10(9):1240-1242
pubmed: 26291007
Mediastinum. 2019 Sep;3:
pubmed: 31608320
BMC Cancer. 2017 Oct 23;17(1):697
pubmed: 29061138
Clin Epigenetics. 2019 Dec 4;11(1):181
pubmed: 31801613