Distinctive phenogroup to differentiate diagnosis of cardiac myxoma vs cardiovascular disease examining blood-based circulating cell biomarkers

Abstract Cardiac myxoma (CM) is a potentially life-threatening disease because frequently asymptomatic or debuts with aspecific manifestations. Definitive diagnosis is established by histopathological assessment including tumor and endothelial cell markers. To derive a specific panel of circulating...

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Main Authors: Giuseppe Donato, Chiara Mignogna, Gianluca Santise, Ivan Presta, Teresa Ferrazzo, Virginia Garo, Daniele Maselli, Antonio Curcio, Salvatore De Rosa, Carmen Spaccarotella, Vincenzo Mollace, Francesco Gentile, Ciro Indolfi, Natalia Malara
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-47639-y
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author Giuseppe Donato
Chiara Mignogna
Gianluca Santise
Ivan Presta
Teresa Ferrazzo
Virginia Garo
Daniele Maselli
Antonio Curcio
Salvatore De Rosa
Carmen Spaccarotella
Vincenzo Mollace
Francesco Gentile
Ciro Indolfi
Natalia Malara
author_facet Giuseppe Donato
Chiara Mignogna
Gianluca Santise
Ivan Presta
Teresa Ferrazzo
Virginia Garo
Daniele Maselli
Antonio Curcio
Salvatore De Rosa
Carmen Spaccarotella
Vincenzo Mollace
Francesco Gentile
Ciro Indolfi
Natalia Malara
author_sort Giuseppe Donato
collection DOAJ
description Abstract Cardiac myxoma (CM) is a potentially life-threatening disease because frequently asymptomatic or debuts with aspecific manifestations. Definitive diagnosis is established by histopathological assessment including tumor and endothelial cell markers. To derive a specific panel of circulating cells antigenically detectable, pre-surgery peripheral blood samples of CM patients were analyzed. Pre-surgery peripheral blood samples from patients with CM were simultaneously analyzed for Circulating tumor cells (CTCs) and circulating endothelial cells (CECs) that were matched with tumor tissue profiles and with patient-derived xenografts (PDXs) distinguishing tumor regions. Moreover, CECs values in CM patients were further matched with CEC’s levels in cardiovascular disease and control subjects. The blood-derived cytological specimens detected at least 1–3 CTCs/ml in 10 tested CM samples (p = 0.0001) showing specific CM features preserved in the central zones of the tumor. The central zone of the primary tumor, supported by a vessel density rate (55 ± 7%), with a proliferative profile of 32 ± 3% and a percentage of Calretininpos cells (p = 0.03), is the principal site of CTCs (r = 00) dissemination. The subsets of endothelial cells recognized in the blood were indifferent to their topological distribution within the tumor and corresponding PDXs. With further refinement and validation in large cohorts, multiparametric liquid biopsies can optimally integrate clinically informative datasets and maximize their utility in pre-surgery evaluation of CM patients. Blood-derived culture’s protocol provides a versatile method capable of viable analysis of CTCs of non-hematological rare tumors which conventional antibody-mediated analytical platform is unable to perform. Distinctive blood- based cell phenotype contributes to differentiate CM from other differentials assuring its prompt surgical resection by combining blood-based cell biomarkers integrated with clinically informative datasets.
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spelling doaj.art-2accb43e797343b1936799b6ea1edcf22023-11-26T13:16:32ZengNature PortfolioScientific Reports2045-23222023-11-011311910.1038/s41598-023-47639-yDistinctive phenogroup to differentiate diagnosis of cardiac myxoma vs cardiovascular disease examining blood-based circulating cell biomarkersGiuseppe Donato0Chiara Mignogna1Gianluca Santise2Ivan Presta3Teresa Ferrazzo4Virginia Garo5Daniele Maselli6Antonio Curcio7Salvatore De Rosa8Carmen Spaccarotella9Vincenzo Mollace10Francesco Gentile11Ciro Indolfi12Natalia Malara13Department of Health Sciences, University “Magna Graecia”Interdipartimentale Service Center, University Magna GraeciaCardiothoracic Surgery Unit, Sant’Anna HospitalDepartment of Health Sciences, University “Magna Graecia”Department of Health Sciences, University “Magna Graecia”Department of Health Sciences, University “Magna Graecia”Cardiothoracic Surgery Unit, Sant’Anna HospitalDepartment of Medical and Surgical Sciences, University Magna GraeciaDepartment of Medical and Surgical Sciences, University Magna GraeciaDepartment of Medical and Surgical Sciences, University Magna GraeciaDepartment of Health Sciences, University “Magna Graecia”Department of Experimental and Clinical Medicine, University Magna GraeciaDepartment of Medical and Surgical Sciences, University Magna GraeciaDepartment of Health Sciences, University “Magna Graecia”Abstract Cardiac myxoma (CM) is a potentially life-threatening disease because frequently asymptomatic or debuts with aspecific manifestations. Definitive diagnosis is established by histopathological assessment including tumor and endothelial cell markers. To derive a specific panel of circulating cells antigenically detectable, pre-surgery peripheral blood samples of CM patients were analyzed. Pre-surgery peripheral blood samples from patients with CM were simultaneously analyzed for Circulating tumor cells (CTCs) and circulating endothelial cells (CECs) that were matched with tumor tissue profiles and with patient-derived xenografts (PDXs) distinguishing tumor regions. Moreover, CECs values in CM patients were further matched with CEC’s levels in cardiovascular disease and control subjects. The blood-derived cytological specimens detected at least 1–3 CTCs/ml in 10 tested CM samples (p = 0.0001) showing specific CM features preserved in the central zones of the tumor. The central zone of the primary tumor, supported by a vessel density rate (55 ± 7%), with a proliferative profile of 32 ± 3% and a percentage of Calretininpos cells (p = 0.03), is the principal site of CTCs (r = 00) dissemination. The subsets of endothelial cells recognized in the blood were indifferent to their topological distribution within the tumor and corresponding PDXs. With further refinement and validation in large cohorts, multiparametric liquid biopsies can optimally integrate clinically informative datasets and maximize their utility in pre-surgery evaluation of CM patients. Blood-derived culture’s protocol provides a versatile method capable of viable analysis of CTCs of non-hematological rare tumors which conventional antibody-mediated analytical platform is unable to perform. Distinctive blood- based cell phenotype contributes to differentiate CM from other differentials assuring its prompt surgical resection by combining blood-based cell biomarkers integrated with clinically informative datasets.https://doi.org/10.1038/s41598-023-47639-y
spellingShingle Giuseppe Donato
Chiara Mignogna
Gianluca Santise
Ivan Presta
Teresa Ferrazzo
Virginia Garo
Daniele Maselli
Antonio Curcio
Salvatore De Rosa
Carmen Spaccarotella
Vincenzo Mollace
Francesco Gentile
Ciro Indolfi
Natalia Malara
Distinctive phenogroup to differentiate diagnosis of cardiac myxoma vs cardiovascular disease examining blood-based circulating cell biomarkers
Scientific Reports
title Distinctive phenogroup to differentiate diagnosis of cardiac myxoma vs cardiovascular disease examining blood-based circulating cell biomarkers
title_full Distinctive phenogroup to differentiate diagnosis of cardiac myxoma vs cardiovascular disease examining blood-based circulating cell biomarkers
title_fullStr Distinctive phenogroup to differentiate diagnosis of cardiac myxoma vs cardiovascular disease examining blood-based circulating cell biomarkers
title_full_unstemmed Distinctive phenogroup to differentiate diagnosis of cardiac myxoma vs cardiovascular disease examining blood-based circulating cell biomarkers
title_short Distinctive phenogroup to differentiate diagnosis of cardiac myxoma vs cardiovascular disease examining blood-based circulating cell biomarkers
title_sort distinctive phenogroup to differentiate diagnosis of cardiac myxoma vs cardiovascular disease examining blood based circulating cell biomarkers
url https://doi.org/10.1038/s41598-023-47639-y
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