EV-associated miRNAs from peritoneal lavage as potential diagnostic biomarkers in colorectal cancer.


Journal

Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741

Informations de publication

Date de publication:
20 06 2019
Historique:
received: 02 04 2019
accepted: 13 06 2019
entrez: 22 6 2019
pubmed: 22 6 2019
medline: 1 7 2020
Statut: epublish

Résumé

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality worldwide. Current systematic methods for diagnosing have inherent limitations so development of a minimally-invasive diagnosis, based on the identification of sensitive biomarkers in liquid biopsies could therefore facilitate screening among population at risk. In this study, we aim to develop a novel approach to identify highly sensitive and specific biomarkers by investigating the use of extracellular vesicles (EVs) isolated from the peritoneal lavage as a source of potential miRNA diagnostic biomarkers. We isolated EVs by ultracentrifugation from 25 ascitic fluids and 25 peritoneal lavages from non-cancer and CRC patients, respectively. Analysis of the expression of EV-associated miRNAs was performed using Taqman OpenArray technology through which we could detect 371 miRNAs. 210 miRNAs were significantly dysregulated (adjusted p value < 0.05 and abs(logFC) ≥ 1). The top-10 miRNAs, which had the AUC value higher than 0.95, were miRNA-199b-5p, miRNA-150-5p, miRNA-29c-5p, miRNA-218-5p, miRNA-99a-3p, miRNA-383-5p, miRNA-199a-3p, miRNA-193a-5p, miRNA-10b-5p and miRNA-181c-5p. This finding opens the avenue to the use of EV-associated miRNA of peritoneal lavages as an untapped source of biomarkers for CRC.

Sections du résumé

BACKGROUND
Colorectal cancer (CRC) is the third leading cause of cancer-related mortality worldwide. Current systematic methods for diagnosing have inherent limitations so development of a minimally-invasive diagnosis, based on the identification of sensitive biomarkers in liquid biopsies could therefore facilitate screening among population at risk.
METHODS
In this study, we aim to develop a novel approach to identify highly sensitive and specific biomarkers by investigating the use of extracellular vesicles (EVs) isolated from the peritoneal lavage as a source of potential miRNA diagnostic biomarkers. We isolated EVs by ultracentrifugation from 25 ascitic fluids and 25 peritoneal lavages from non-cancer and CRC patients, respectively. Analysis of the expression of EV-associated miRNAs was performed using Taqman OpenArray technology through which we could detect 371 miRNAs.
RESULTS
210 miRNAs were significantly dysregulated (adjusted p value < 0.05 and abs(logFC) ≥ 1). The top-10 miRNAs, which had the AUC value higher than 0.95, were miRNA-199b-5p, miRNA-150-5p, miRNA-29c-5p, miRNA-218-5p, miRNA-99a-3p, miRNA-383-5p, miRNA-199a-3p, miRNA-193a-5p, miRNA-10b-5p and miRNA-181c-5p.
CONCLUSIONS
This finding opens the avenue to the use of EV-associated miRNA of peritoneal lavages as an untapped source of biomarkers for CRC.

Identifiants

pubmed: 31221189
doi: 10.1186/s12967-019-1954-8
pii: 10.1186/s12967-019-1954-8
pmc: PMC6585099
doi:

Substances chimiques

Biomarkers, Tumor 0
MicroRNAs 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

208

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Auteurs

Berta Roman-Canal (B)

Department of Pathology and Molecular Genetics/Oncologic Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), University of Lleida, CIBERONC, Lleida, Spain.
Department of Pathology, University Hospital of Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.

Jordi Tarragona (J)

Department of Pathology and Molecular Genetics/Oncologic Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), University of Lleida, CIBERONC, Lleida, Spain.

Cristian Pablo Moiola (CP)

Department of Pathology and Molecular Genetics/Oncologic Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), University of Lleida, CIBERONC, Lleida, Spain.
Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, CIBERONC, Pg. Vall Hebron 119-129, 08035, Barcelona, Spain.

Sònia Gatius (S)

Department of Pathology and Molecular Genetics/Oncologic Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), University of Lleida, CIBERONC, Lleida, Spain.

Sarah Bonnin (S)

Centre for Genomic Regulation (CRG), The Barcelona Institute or Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain.

Maria Ruiz-Miró (M)

Department of Pathology and Molecular Genetics/Oncologic Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), University of Lleida, CIBERONC, Lleida, Spain.

José Enrique Sierra (JE)

Department of Surgery, Hospital Arnau de Vilanova, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain.

Maria Rufas (M)

Department of Surgery, Hospital Arnau de Vilanova, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain.

Esperanza González (E)

Exosomes Laboratory and Metabolomics Platform, CIC bioGUNE, CIBEREHD Bizkaia Technology Park, Derio, Spain.

José M Porcel (JM)

Pleural Medicine Unit, Arnau de Vilanova University Hospital, IRBLleida, Lleida, Spain.

Antonio Gil-Moreno (A)

Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, CIBERONC, Pg. Vall Hebron 119-129, 08035, Barcelona, Spain.
Gynecological Oncology Department, Vall Hebron University Hospital, CIBERONC, Barcelona, Spain.

Juan M Falcón-Pérez (JM)

Exosomes Laboratory and Metabolomics Platform, CIC bioGUNE, CIBEREHD Bizkaia Technology Park, Derio, Spain.
IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain.

Julia Ponomarenko (J)

Centre for Genomic Regulation (CRG), The Barcelona Institute or Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain.
University Pompeu Fabra, Barcelona, Spain.

Xavier Matias-Guiu (X)

Department of Pathology and Molecular Genetics/Oncologic Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), University of Lleida, CIBERONC, Lleida, Spain. fjmatiasguiu.lleida.ics@gencat.cat.
Department of Pathology, University Hospital of Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. fjmatiasguiu.lleida.ics@gencat.cat.
Oncologic Pathology Group, Department of Medicine UdL, Biomedical Research Institute of Lleida (IrbLleida), Av. Rovira Roure 80, 25198, Lleida, Spain. fjmatiasguiu.lleida.ics@gencat.cat.

Eva Colas (E)

Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, CIBERONC, Pg. Vall Hebron 119-129, 08035, Barcelona, Spain. eva.colas@vhir.org.

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