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Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

dc.contributor.authorLapitz Dambolenea, Ainhoa
dc.contributor.authorArbelaiz Cossio, Ander
dc.contributor.authorO’Rourke, Colm J.
dc.contributor.authorLavín, José L.
dc.contributor.authorCasta, Adelaida La
dc.contributor.authorIbarra, Cesar
dc.contributor.authorJimeno, Juan P.
dc.contributor.authorSantos Laso, Álvaro
dc.contributor.authorIzquierdo Sánchez, Laura
dc.contributor.authorKrawczyk, Marcin
dc.contributor.authorPerugorria Montiel, María Jesús
dc.contributor.authorJiménez Agüero, Raúl
dc.contributor.authorSanchez-Campos, Alberto
dc.contributor.authorRiaño Fernández, Ioana
dc.contributor.authorGónzalez, Esperanza
dc.contributor.authorLammert, Frank
dc.contributor.authorMarzioni, Marco
dc.contributor.authorRodríguez Macías, Rocío Isabel
dc.contributor.authorGarcía Marín, Jose Juan
dc.contributor.authorKarlsen, Tom H.
dc.contributor.authorBujanda Fernández de Pierola, Luis ORCID
dc.contributor.authorFalcón Pérez, Juan Manuel
dc.contributor.authorAndersen, Jesper B.
dc.contributor.authorAransay Bañares, Ana María
dc.contributor.authorRodrigues, Pedro M.
dc.contributor.authorBañales Asurmendi, Jesús María ORCID
dc.date.accessioned2020-04-03T16:38:55Z
dc.date.available2020-04-03T16:38:55Z
dc.date.issued2020-03-14
dc.identifier.citationCells 9(3) : (2020) // Article ID 721es_ES
dc.identifier.issn2073-4409
dc.identifier.urihttp://hdl.handle.net/10810/42599
dc.description.abstractCholangiocarcinoma (CCA) comprises a group of heterogeneous biliary cancers with dismal prognosis. The etiologies of most CCAs are unknown, but primary sclerosing cholangitis (PSC) is a risk factor. Non-invasive diagnosis of CCA is challenging and accurate biomarkers are lacking. We aimed to characterize the transcriptomic profile of serum and urine extracellular vesicles (EVs) from patients with CCA, PSC, ulcerative colitis (UC), and healthy individuals. Serum and urine EVs were isolated by serial ultracentrifugations and characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting. EVs transcriptome was determined by Illumina gene expression array [messenger RNAs (mRNA) and non-coding RNAs (ncRNAs)]. Differential RNA profiles were found in serum and urine EVs from patients with CCA compared to control groups (disease and healthy), showing high diagnostic capacity. The comparison of the mRNA profiles of serum or urine EVs from patients with CCA with the transcriptome of tumor tissues from two cohorts of patients, CCA cells in vitro, and CCA cells-derived EVs, identified 105 and 39 commonly-altered transcripts, respectively. Gene ontology analysis indicated that most commonly-altered mRNAs participate in carcinogenic steps. Overall, patients with CCA present specific RNA profiles in EVs mirroring the tumor, and constituting novel promising liquid biopsy biomarkers.es_ES
dc.description.sponsorshipThis research was funded by Spanish Carlos III Health Institute (ISCIII) [J.M. Banales (FIS PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129; M.J. Perugorria: PI14/00399, PI17/00022; J.J.G. Marin: FIS PI16/00598 and PI19/00819; P.M. Rodrigues: Sara Borrell CD19/00254] cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER); CIBERehd (ISCIII): J.M. Banales, M.J. Perugorria, L. Bujanda and J.J.G. Marin; Spanish Ministry of Economy and Competitiveness (M.J. Perugorria: Ramon y Cajal Programme RYC-2015-17755); AMMF (J.M. Banales and P.M. Rodrigues 2019/202); PSC Partners US (J.M. Banales); PSC Supports UK (J.M. Banales: 06119JB); Horizon 2020 (J.M. Banales: H2020 ESCALON project: H2020-SC1-BHC-2018-2020); IKERBASQUE, Basque foundation for Science (M.J. Perugorria and J.M. Banales), Spain; “Junta de Castilla y Leon” (J.J.G. Marin: SA06P17); “Diputación Foral Gipuzkoa” (J.M. Banales: DFG15/010, DFG16/004; M.J. Perugorria: DFG18/114, DFG19/081), BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD to J.M. Banales), Department of Health of the Basque Country (L. Bujanda: 2013111173; J.M. Banales: 2017111010) and Euskadi RIS3 (J.M. Banales: 2016222001, 2017222014, 2018222029; 2019222054). La Caixa Scientific Foundation (J.M. Banales: HR17-00601). “Fundación Científica de la Asociación Española Contra el Cáncer” (AECC Scientific Foundation, to J.M. Banales and J.J.G. Marin). “Centro Internacional sobre el Envejecimiento”, Spain (R.I.R. Macias: OLD-HEPAMARKER, 0348-CIE-6-E). A. Lapitz and A Santos-Laso were funded by the Basque Government (PRE_2018_2_0195 and PRE_2015_1_0126, respectively). J.B. Andersen is supported by the Danish Medical Research Council, Danish Cancer Society, Novo Nordisk Foundation, and A.P. Møller Foundation. C.J. O’Rourke is supported by Marie Skłodowska -Curie Program.es_ES
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/825510es_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/RYC-2015-17755es_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/
dc.subjectbiomarkerses_ES
dc.subjectcholangiocarcinomaes_ES
dc.subjectextracellular vesicleses_ES
dc.subjectliquid biopsyes_ES
dc.subjecttranscriptomicses_ES
dc.titlePatients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosises_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.date.updated2020-03-27T14:53:47Z
dc.rights.holder© 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/)es_ES
dc.relation.publisherversionhttps://www.mdpi.com/2073-4409/9/3/721es_ES
dc.identifier.doi10.3390/cells9030721
dc.contributor.funderEuropean Commission
dc.departamentoesMedicina
dc.departamentoesCirugía, radiología y medicina física
dc.departamentoeuMedikuntza
dc.departamentoeuKirurgia,erradiologia eta medikuntza fisikoa


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© 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/)
Except where otherwise noted, this item's license is described as © 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/)