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

Ainhoa Lapitz; Ander Arbelaiz; Colm J. O’Rourke; Jose L. Lavin; Adelaida La Casta; Cesar Ibarra; Juan P. Jimeno; Alvaro Santos-Laso; Laura Izquierdo-Sanchez; Marcin Krawczyk; Maria J. Perugorria; Raul Jimenez-Aguero; Alberto Sanchez-Campos; Ioana Riaño; Esperanza Gónzalez; Frank Lammert; Marco Marzioni; Rocio I.R. Macias; Jose J. G. Marin; Tom H. Karlsen; Luis Bujanda; Juan M. Falcón-Pérez; Jesper B. Andersen; Ana M. Aransay; Pedro M. Rodrigues; Jesus M. Banales

doi:10.3390/cells9030721

Cells (Mar 2020)

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

Ainhoa Lapitz,
Ander Arbelaiz,
Colm J. O’Rourke,
Jose L. Lavin,
Adelaida La Casta,
Cesar Ibarra,
Juan P. Jimeno,
Alvaro Santos-Laso,
Laura Izquierdo-Sanchez,
Marcin Krawczyk,
Maria J. Perugorria,
Raul Jimenez-Aguero,
Alberto Sanchez-Campos,
Ioana Riaño,
Esperanza Gónzalez,
Frank Lammert,
Marco Marzioni,
Rocio I.R. Macias,
Jose J. G. Marin,
Tom H. Karlsen,
Luis Bujanda,
Juan M. Falcón-Pérez,
Jesper B. Andersen,
Ana M. Aransay,
Pedro M. Rodrigues,
Jesus M. Banales

Affiliations

Ainhoa Lapitz: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain
Ander Arbelaiz: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain
Colm J. O’Rourke: Biotech Research & Innovation Centre (BRIC), Department of Health and Medical Sciences, 2200, Copenhagen, Denmark
Jose L. Lavin: CIC bioGUNE, Genome Analysis Platform, 48160, Derio, Spain
Adelaida La Casta: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain
Cesar Ibarra: Hospital of Cruces, 48903, Bilbao, Spain
Juan P. Jimeno: “Complejo Hospitalario de Navarra”, 31008, Pamplona, Spain
Alvaro Santos-Laso: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain
Laura Izquierdo-Sanchez: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain
Marcin Krawczyk: Department of Medicine II, Saarland University Medical Centre, Saarland University, 66421, Homburg, Germany
Maria J. Perugorria: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain
Raul Jimenez-Aguero: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain
Alberto Sanchez-Campos: Hospital of Cruces, 48903, Bilbao, Spain
Ioana Riaño: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain
Esperanza Gónzalez: Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Exosomes Laboratory, 48160, Derio, Spain
Frank Lammert: Department of Medicine II, Saarland University Medical Centre, Saarland University, 66421, Homburg, Germany
Marco Marzioni: “Università Politecnica delle Marche”, Department of Gastroenterology, 60121, Ancona, Italy
Rocio I.R. Macias: Carlos III National Institute of Health, Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), 28220, Madrid, Spain
Jose J. G. Marin: Carlos III National Institute of Health, Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), 28220, Madrid, Spain
Tom H. Karlsen: Norwegian PSC Research Center, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, 0372, Oslo, Spain
Luis Bujanda: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain
Juan M. Falcón-Pérez: Carlos III National Institute of Health, Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), 28220, Madrid, Spain
Jesper B. Andersen: Biotech Research & Innovation Centre (BRIC), Department of Health and Medical Sciences, 2200, Copenhagen, Denmark
Ana M. Aransay: CIC bioGUNE, Genome Analysis Platform, 48160, Derio, Spain
Pedro M. Rodrigues: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain
Jesus M. Banales: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain

DOI: https://doi.org/10.3390/cells9030721
Journal volume & issue: Vol. 9, no. 3
p. 721

Abstract

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: 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.

Published in Cells

ISSN: 2073-4409 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Cytology
Website: https://www.mdpi.com/journal/cells

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