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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

1
Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain
2
Biotech Research & Innovation Centre (BRIC), Department of Health and Medical Sciences, 2200, Copenhagen, Denmark
3
CIC bioGUNE, Genome Analysis Platform, 48160, Derio, Spain
4
Hospital of Cruces, 48903, Bilbao, Spain
5
“Complejo Hospitalario de Navarra”, 31008, Pamplona, Spain
6
Carlos III National Institute of Health, Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), 28220, Madrid, Spain
7
Department of Medicine II, Saarland University Medical Centre, Saarland University, 66421, Homburg, Germany
8
Laboratory of Metabolic Liver Diseases, Centre for Preclinical Research, Department of General, Transplant and Liver Surgery, 02-091, Warsaw, Poland
9
Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Exosomes Laboratory, 48160, Derio, Spain
10
“Università Politecnica delle Marche”, Department of Gastroenterology, 60121, Ancona, Italy
11
Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), 37007, Salamanca, Spain
12
Norwegian PSC Research Center, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, 0372, Oslo, Spain
13
IKERBASQUE, Basque Foundation for Science, 48013, Bilbao, Spain
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(3), 721; https://doi.org/10.3390/cells9030721
Received: 17 February 2020 / Revised: 6 March 2020 / Accepted: 9 March 2020 / Published: 14 March 2020
: 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. View Full-Text
Keywords: biomarkers; cholangiocarcinoma; extracellular vesicles; liquid biopsy; transcriptomics biomarkers; cholangiocarcinoma; extracellular vesicles; liquid biopsy; transcriptomics
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Lapitz, A.; Arbelaiz, A.; O’Rourke, C.J.; Lavin, J.L.; Casta, A.L.; Ibarra, C.; Jimeno, J.P.; Santos-Laso, A.; Izquierdo-Sanchez, L.; Krawczyk, M.; Perugorria, M.J.; Jimenez-Aguero, R.; Sanchez-Campos, A.; Riaño, I.; Gónzalez, E.; Lammert, F.; Marzioni, M.; Macias, R.I.; Marin, J.J.G.; Karlsen, T.H.; Bujanda, L.; Falcón-Pérez, J.M.; Andersen, J.B.; Aransay, A.M.; Rodrigues, P.M.; Banales, J.M. Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis. Cells 2020, 9, 721.

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