Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis
Fecha
2020-03-14Autor
Lapitz Dambolenea, Ainhoa
Arbelaiz Cossio, Ander
O’Rourke, Colm J.
Lavín, José L.
Casta, Adelaida La
Ibarra, Cesar
Jimeno, Juan P.
Santos Laso, Álvaro
Izquierdo Sánchez, Laura
Krawczyk, Marcin
Perugorria Montiel, María Jesús
Jiménez Agüero, Raúl
Sanchez-Campos, Alberto
Riaño Fernández, Ioana
Gónzalez, Esperanza
Lammert, Frank
Marzioni, Marco
Rodríguez Macías, Rocío Isabel
García Marín, Jose Juan
Karlsen, Tom H.
Falcón Pérez, Juan Manuel
Andersen, Jesper B.
Aransay Bañares, Ana María
Rodrigues, Pedro M.
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Cells 9(3) : (2020) // Article ID 721
Resumen
Cholangiocarcinoma (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.
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