Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure
Background & Aims: MicroRNAs (miRNAs) circulate in several body fluids and can be useful biomarkers. The aim of this study was to identify blood-circulating miRNAs associated with cirrhosis progression and acute-on-chronic liver failure (ACLF). Methods: Using high-throughput screening of 754...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-04-01
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| Series: | JHEP Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555921000094 |
| _version_ | 1818678174583619584 |
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| author | Delia Blaya Elisa Pose Mar Coll Juan José Lozano Isabel Graupera Robert Schierwagen Christian Jansen Pedro Castro Sara Fernandez Julia Sidorova Mariuca Vasa-Nicotera Elsa Solà Joan Caballería Jonel Trebicka Pere Ginès Pau Sancho-Bru |
| author_facet | Delia Blaya Elisa Pose Mar Coll Juan José Lozano Isabel Graupera Robert Schierwagen Christian Jansen Pedro Castro Sara Fernandez Julia Sidorova Mariuca Vasa-Nicotera Elsa Solà Joan Caballería Jonel Trebicka Pere Ginès Pau Sancho-Bru |
| author_sort | Delia Blaya |
| collection | DOAJ |
| description | Background & Aims: MicroRNAs (miRNAs) circulate in several body fluids and can be useful biomarkers. The aim of this study was to identify blood-circulating miRNAs associated with cirrhosis progression and acute-on-chronic liver failure (ACLF). Methods: Using high-throughput screening of 754 miRNAs, serum samples from 45 patients with compensated cirrhosis, decompensated cirrhosis, or ACLF were compared with those from healthy individuals (n = 15). miRNA levels were correlated with clinical parameters, organ failure, and disease progression and outcome. Dysregulated miRNAs were evaluated in portal and hepatic vein samples (n = 33), liver tissues (n = 17), and peripheral blood mononuclear cells (PBMCs) (n = 16). Results: miRNA screening analysis revealed that circulating miRNAs are dysregulated in cirrhosis progression, with 51 miRNAs being differentially expressed among all groups of patients. Unsupervised clustering and principal component analysis indicated that the main differences in miRNA expression occurred at decompensation, showing similar levels in patients with decompensated cirrhosis and those with ACLF. Of 43 selected miRNAs examined for differences among groups, 10 were differentially expressed according to disease progression. Moreover, 20 circulating miRNAs were correlated with model for end-stage liver disease and Child-Pugh scores. Notably, 11 dysregulated miRNAs were associated with kidney or liver failure, encephalopathy, bacterial infection, and poor outcomes. The most severely dysregulated miRNAs (i.e. miR-146a-5p, miR-26a-5p, and miR-191-5p) were further evaluated in portal and hepatic vein blood and liver tissue, but showed no differences. However, PBMCs from patients with cirrhosis showed significant downregulation of miR-26 and miR-146a, suggesting a extrahepatic origin of some circulating miRNAs. Conclusions: This study is a repository of circulating miRNA data following cirrhosis progression and ACLF. Circulating miRNAs were profoundly dysregulated during the progression of chronic liver disease, were associated with failure of several organs and could have prognostic utility. Lay summary: Circulating miRNAs are small molecules in the blood that can be used to identify or predict a clinical condition. Our study aimed to identify miRNAs for use as biomarkers in patients with cirrhosis or acute-on-chronic liver failure. Several miRNAs were found to be dysregulated during the progression of disease, and some were also related to organ failure and disease-related outcomes. |
| first_indexed | 2024-12-17T09:11:04Z |
| format | Article |
| id | doaj.art-b58b7a66ed174809bfc0f1e51931249b |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-12-17T09:11:04Z |
| publishDate | 2021-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-b58b7a66ed174809bfc0f1e51931249b2022-12-21T21:55:12ZengElsevierJHEP Reports2589-55592021-04-0132100233Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failureDelia Blaya0Elisa Pose1Mar Coll2Juan José Lozano3Isabel Graupera4Robert Schierwagen5Christian Jansen6Pedro Castro7Sara Fernandez8Julia Sidorova9Mariuca Vasa-Nicotera10Elsa Solà11Joan Caballería12Jonel Trebicka13Pere Ginès14Pau Sancho-Bru15Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Liver Unit, Hospital Clinic of Barcelona, Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Liver Unit, Hospital Clinic of Barcelona, Barcelona, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Liver Unit, Hospital Clinic of Barcelona, Barcelona, SpainGoethe University Clinic, Frankfurt, GermanyUniversity Clinic Bonn, Bonn, GermanyMedical Intensive Care Unit, Hospital Clinic of Barcelona, IDIBAPS, University of Barcelona, Barcelona, SpainMedical Intensive Care Unit, Hospital Clinic of Barcelona, IDIBAPS, University of Barcelona, Barcelona, SpainInstituto de Tecnología del Conocimiento (ITC). Campus de Somosaguas, Universidad Complutense de Madrid (UCM), SpainGoethe University Clinic, Frankfurt, GermanyInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Liver Unit, Hospital Clinic of Barcelona, Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Liver Unit, Hospital Clinic of Barcelona, Barcelona, SpainGoethe University Clinic, Frankfurt, Germany; European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain; Institute for Bioengineering of Catalonia, Barcelona, Spain; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Internal Medicine I, University Clinic Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany. Tel.: +34 93 227 14 11; Fax: +34 93 227 14 19Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Liver Unit, Hospital Clinic of Barcelona, Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Corresponding authors. Addresses: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), C/ Rosselló, 149-153, third floor, 08036, Barcelona, Spain. Tel.: +34 93 227 54 00 ext. 3371.Background & Aims: MicroRNAs (miRNAs) circulate in several body fluids and can be useful biomarkers. The aim of this study was to identify blood-circulating miRNAs associated with cirrhosis progression and acute-on-chronic liver failure (ACLF). Methods: Using high-throughput screening of 754 miRNAs, serum samples from 45 patients with compensated cirrhosis, decompensated cirrhosis, or ACLF were compared with those from healthy individuals (n = 15). miRNA levels were correlated with clinical parameters, organ failure, and disease progression and outcome. Dysregulated miRNAs were evaluated in portal and hepatic vein samples (n = 33), liver tissues (n = 17), and peripheral blood mononuclear cells (PBMCs) (n = 16). Results: miRNA screening analysis revealed that circulating miRNAs are dysregulated in cirrhosis progression, with 51 miRNAs being differentially expressed among all groups of patients. Unsupervised clustering and principal component analysis indicated that the main differences in miRNA expression occurred at decompensation, showing similar levels in patients with decompensated cirrhosis and those with ACLF. Of 43 selected miRNAs examined for differences among groups, 10 were differentially expressed according to disease progression. Moreover, 20 circulating miRNAs were correlated with model for end-stage liver disease and Child-Pugh scores. Notably, 11 dysregulated miRNAs were associated with kidney or liver failure, encephalopathy, bacterial infection, and poor outcomes. The most severely dysregulated miRNAs (i.e. miR-146a-5p, miR-26a-5p, and miR-191-5p) were further evaluated in portal and hepatic vein blood and liver tissue, but showed no differences. However, PBMCs from patients with cirrhosis showed significant downregulation of miR-26 and miR-146a, suggesting a extrahepatic origin of some circulating miRNAs. Conclusions: This study is a repository of circulating miRNA data following cirrhosis progression and ACLF. Circulating miRNAs were profoundly dysregulated during the progression of chronic liver disease, were associated with failure of several organs and could have prognostic utility. Lay summary: Circulating miRNAs are small molecules in the blood that can be used to identify or predict a clinical condition. Our study aimed to identify miRNAs for use as biomarkers in patients with cirrhosis or acute-on-chronic liver failure. Several miRNAs were found to be dysregulated during the progression of disease, and some were also related to organ failure and disease-related outcomes.http://www.sciencedirect.com/science/article/pii/S2589555921000094Liver decompensationNon-coding RNAsBiomarkersChronic liver disease |
| spellingShingle | Delia Blaya Elisa Pose Mar Coll Juan José Lozano Isabel Graupera Robert Schierwagen Christian Jansen Pedro Castro Sara Fernandez Julia Sidorova Mariuca Vasa-Nicotera Elsa Solà Joan Caballería Jonel Trebicka Pere Ginès Pau Sancho-Bru Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure JHEP Reports Liver decompensation Non-coding RNAs Biomarkers Chronic liver disease |
| title | Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure |
| title_full | Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure |
| title_fullStr | Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure |
| title_full_unstemmed | Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure |
| title_short | Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure |
| title_sort | profiling circulating micrornas in patients with cirrhosis and acute on chronic liver failure |
| topic | Liver decompensation Non-coding RNAs Biomarkers Chronic liver disease |
| url | http://www.sciencedirect.com/science/article/pii/S2589555921000094 |
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