Liquid biopsy of patients with advanced liver fibrosis reveals the association of methylation in CpGs and miRNAs expression with the degree of severity

Introduction and Objective: This study aimed to assess whether the expression of specific miRNAs and the percentage of DNA methylation of the Peroxisomal Proliferator-Activated Receptors (PPAR) α, γ and δ genes in tissue and liquid biopsy from patients with advanced liver fibrosis (F3 and F4) is ass...

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Main Authors: R De la Rosa-Bibiano, R Escutia-Gutiérrez, S Rodríguez-Sanabria, E Cerda-Reyes, JM Aguilar, A Santos, AS Sandoval-Rodríguez, J Armendáriz-Borunda
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Annals of Hepatology
Online Access:http://www.sciencedirect.com/science/article/pii/S1665268122001338
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author R De la Rosa-Bibiano
R Escutia-Gutiérrez
S Rodríguez-Sanabria
E Cerda-Reyes
JM Aguilar
A Santos
AS Sandoval-Rodríguez
J Armendáriz-Borunda
author_facet R De la Rosa-Bibiano
R Escutia-Gutiérrez
S Rodríguez-Sanabria
E Cerda-Reyes
JM Aguilar
A Santos
AS Sandoval-Rodríguez
J Armendáriz-Borunda
author_sort R De la Rosa-Bibiano
collection DOAJ
description Introduction and Objective: This study aimed to assess whether the expression of specific miRNAs and the percentage of DNA methylation of the Peroxisomal Proliferator-Activated Receptors (PPAR) α, γ and δ genes in tissue and liquid biopsy from patients with advanced liver fibrosis (F3 and F4) is associated to the degree of severity. Materials and methods: Transjugular liver biopsy and liquid biopsy were collected from 23 patients with sustained viral response to the hepatitis C virus, with advanced residual fibrosis (F3 and F4). The percentage of methylation in CpG islands of the promoters of the PPARα, PPARγ and PPARδ genes and the expression levels of miRNAs were determined. Masson's trichrome hematoxylin-eosin staining was performed. DNA was extracted from tissues and plasma, and percent methylation was measured by pyrosequencing. Extraction and isolation of miRNAs from liver tissue were performed: miR-21, miR-34, miR-122, miR181b, miR192, miR-200a/b and their expression level compared to miR-16 was evaluated. The trial was approved by the research ethics committee, and informed consent was obtained. Results: Higher promoter methylation percentages were observed in patients with more severe degrees of fibrosis (F4), both in tissue and in liquid biopsy. In addition, overexpression of miRNAs was associated with the degree of fibrosis. Discussion: Epigenetic mechanisms (DNA methylation and microRNA expression) regulate the expression of multiple genes and their status may be a biomarker associated with the degree of fibrosis. Conclusion: Liquid biopsy is an effective and accessible method for evaluating the degree of fibrosis. Funding: The resources used in this study were from the hospital without any additional financing Declaration of interest: The authors declare no potential conflicts of interest.
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spelling doaj.art-3166271da3b6489a9f8d233ed5414a012022-12-22T02:46:10ZengElsevierAnnals of Hepatology1665-26812022-12-0127100791Liquid biopsy of patients with advanced liver fibrosis reveals the association of methylation in CpGs and miRNAs expression with the degree of severityR De la Rosa-Bibiano0R Escutia-Gutiérrez1S Rodríguez-Sanabria2E Cerda-Reyes3JM Aguilar4A Santos5AS Sandoval-Rodríguez6J Armendáriz-Borunda7Institute of Molecular Biology in Medicine. CUCS. University of Guadalajara; Hospital Central MilitarInstitute of Molecular Biology in Medicine. CUCS. University of GuadalajaraInstitute of Molecular Biology in Medicine. CUCS. University of GuadalajaraHospital Central MilitarHospital Central MilitarFaculty of Medicine and Health Sciences. Tecnológico de Monterrey. Zapopan, Guadalajara, MexicoInstitute of Molecular Biology in Medicine. CUCS. University of GuadalajaraInstitute of Molecular Biology in Medicine. CUCS. University of Guadalajara; Faculty of Medicine and Health Sciences. Tecnológico de Monterrey. Zapopan, Guadalajara, Mexico; Departments of Gastroenterology, Radiology, Pathology and Clinical Laboratory. Central Military Hospital. MexicoIntroduction and Objective: This study aimed to assess whether the expression of specific miRNAs and the percentage of DNA methylation of the Peroxisomal Proliferator-Activated Receptors (PPAR) α, γ and δ genes in tissue and liquid biopsy from patients with advanced liver fibrosis (F3 and F4) is associated to the degree of severity. Materials and methods: Transjugular liver biopsy and liquid biopsy were collected from 23 patients with sustained viral response to the hepatitis C virus, with advanced residual fibrosis (F3 and F4). The percentage of methylation in CpG islands of the promoters of the PPARα, PPARγ and PPARδ genes and the expression levels of miRNAs were determined. Masson's trichrome hematoxylin-eosin staining was performed. DNA was extracted from tissues and plasma, and percent methylation was measured by pyrosequencing. Extraction and isolation of miRNAs from liver tissue were performed: miR-21, miR-34, miR-122, miR181b, miR192, miR-200a/b and their expression level compared to miR-16 was evaluated. The trial was approved by the research ethics committee, and informed consent was obtained. Results: Higher promoter methylation percentages were observed in patients with more severe degrees of fibrosis (F4), both in tissue and in liquid biopsy. In addition, overexpression of miRNAs was associated with the degree of fibrosis. Discussion: Epigenetic mechanisms (DNA methylation and microRNA expression) regulate the expression of multiple genes and their status may be a biomarker associated with the degree of fibrosis. Conclusion: Liquid biopsy is an effective and accessible method for evaluating the degree of fibrosis. Funding: The resources used in this study were from the hospital without any additional financing Declaration of interest: The authors declare no potential conflicts of interest.http://www.sciencedirect.com/science/article/pii/S1665268122001338
spellingShingle R De la Rosa-Bibiano
R Escutia-Gutiérrez
S Rodríguez-Sanabria
E Cerda-Reyes
JM Aguilar
A Santos
AS Sandoval-Rodríguez
J Armendáriz-Borunda
Liquid biopsy of patients with advanced liver fibrosis reveals the association of methylation in CpGs and miRNAs expression with the degree of severity
Annals of Hepatology
title Liquid biopsy of patients with advanced liver fibrosis reveals the association of methylation in CpGs and miRNAs expression with the degree of severity
title_full Liquid biopsy of patients with advanced liver fibrosis reveals the association of methylation in CpGs and miRNAs expression with the degree of severity
title_fullStr Liquid biopsy of patients with advanced liver fibrosis reveals the association of methylation in CpGs and miRNAs expression with the degree of severity
title_full_unstemmed Liquid biopsy of patients with advanced liver fibrosis reveals the association of methylation in CpGs and miRNAs expression with the degree of severity
title_short Liquid biopsy of patients with advanced liver fibrosis reveals the association of methylation in CpGs and miRNAs expression with the degree of severity
title_sort liquid biopsy of patients with advanced liver fibrosis reveals the association of methylation in cpgs and mirnas expression with the degree of severity
url http://www.sciencedirect.com/science/article/pii/S1665268122001338
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