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Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study

2024-02-24Artigo científico Acesso aberto
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datacite.subject.fosCiências Médicas::Ciências da Saúde
datacite.subject.fosCiências Naturais::Ciências Biológicas
dc.contributor.authorFebra, Claúdia
dc.contributor.authorSaraiva, Joana
dc.contributor.authorVaz, Fátima
dc.contributor.authorSoares, Nelson
dc.contributor.authorPenque, Penque
dc.date.accessioned2025-02-18T15:33:11Z
dc.date.available2025-02-18T15:33:11Z
dc.date.issued2024-02-24
dc.descriptionClinical Trial
dc.description.abstractBackground: Venous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE. Methods: This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was D-glutamine and D-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3',5'-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68). Conclusions: Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.eng
dc.description.sponsorshipThe project was supported by the Instituto Nacional de Saúde de Dr Ricardo Jorge (INSA I.P), ToxOmics-Centre for Toxicogenomics and Human Health (FCT-UID/BIM/00009/2013), RNEM-National Mass Spectrometry Networking-FCT Strategic Infrastructure (LISBOA-01-0145-FEDER-022125 • POCI-01-0145-FEDER-022125) and Fundação para a Ciência e a Tecnologia (FCT)- Fellowship 202214435.BD. This works was also partially financed by Targeted Research Project 2301110175 UOS.
dc.identifier.citationJ Transl Med. 2024 Feb 24;22(1):200. doi: 10.1186/s12967-024-04883-8
dc.identifier.doi10.1186/s12967-024-04883-8
dc.identifier.eissn1479-5876
dc.identifier.pmid38402378
dc.identifier.urihttp://hdl.handle.net/10400.18/10360
dc.language.isoeng
dc.peerreviewedyes
dc.publisherBioMed Central
dc.relationCentre for Toxicogenomics and Human Health
dc.relation.hasversionhttps://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-04883-8
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectMetabolomics
dc.subjectDeep Vein Thrombosis
dc.subjectPulmonary Embolism
dc.subjectVenous Thromboembolism
dc.subjectGenómina Funcional e Estrutural
dc.titleAcute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical studyeng
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCentre for Toxicogenomics and Human Health
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIM%2F00009%2F2013/PT
oaire.citation.startPage200
oaire.citation.titleJournal of Translational Medicine
oaire.citation.volume22
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
relation.isProjectOfPublicationa803b42a-2bae-48f9-88fc-fe2281aa7075
relation.isProjectOfPublication.latestForDiscoverya803b42a-2bae-48f9-88fc-fe2281aa7075

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