Víctor José Asensio1, Anna Tomás1, Amanda Iglesias2, Luis Pérez de Llano3, Victoria Del Pozo4, Borja G Cosío5. 1. Institut d'Investigació Sanitària Illes Balears (IdISBa), Palma de Mallorca, Spain. 2. Institut d'Investigació Sanitària Illes Balears (IdISBa), Palma de Mallorca, Spain; CIBER de Enfermedades Respiratorias, CIBERES, Spain. 3. Department of Respiratory Medicine, Hospital Lucus Augusti, Lugo, Spain. 4. CIBER de Enfermedades Respiratorias, CIBERES, Spain; Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain. 5. Institut d'Investigació Sanitària Illes Balears (IdISBa), Palma de Mallorca, Spain; CIBER de Enfermedades Respiratorias, CIBERES, Spain; Department of Respiratory Medicine, Hospital Universitario Son Espases, Palma de Mallorca, Spain; Clinica Rotger Quiron, Palma de Mallorca, Spain. Electronic address: borja.cosio@ssib.es.
Abstract
BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are common chronic airway diseases that may overlap in some individuals. Asthma COPD overlap (ACO) is a heterogeneous conditions that includes smoking-asthma (SA) and COPD with eosinophilia (COPDe). MicroRNAs (miRNA) are regulators of gene expression with a great potential as biomarkers. OBJECTIVES: The objective of this study was to identify distinctive miRNA signatures in patients from the whole spectrum of chronic obstructive bronchial disease (SA, COPDe, non-smoking asthmatics (NSA), and COPD) that could serve as diagnostic biomarkers or describe differential molecular mechanisms with potential therapeutic implications. METHODS: From a previously characterized cohort of ACO, COPD and asthma patients, we selected a discovery group of 40 patients for miRNA expression profiling by means of microarray technology. Differential expression of miRNAs were validated by quantitative PCR in the complete cohort (n=274). RESULTS: Thirty differentially expressed miRNAs (eBAYES p<0.05, fold change ≥2) were found among the different groups of patients regarding COPDe: 19 COPD-vs-COPDe, 13 NSA-vs-COPDe, 11 SA-vs-COPDe. A characteristic down-regulated miRNA expression pattern was identified in COPDe patients. Differential expression of miR-619-5p and miR-4486 in COPDe patients were validated in the complete cohort (n=274). CONCLUSIONS: We postulate that COPDe patients show a characteristic expression profile of miRNAs distinctive from asthma and COPD. Also that SA and COPDe patients, which have been typically clustered in the ACO group, display distinct molecular events.
BACKGROUND:Asthma and chronic obstructive pulmonary disease (COPD) are common chronic airway diseases that may overlap in some individuals. AsthmaCOPD overlap (ACO) is a heterogeneous conditions that includes smoking-asthma (SA) and COPD with eosinophilia (COPDe). MicroRNAs (miRNA) are regulators of gene expression with a great potential as biomarkers. OBJECTIVES: The objective of this study was to identify distinctive miRNA signatures in patients from the whole spectrum of chronic obstructive bronchial disease (SA, COPDe, non-smoking asthmatics (NSA), and COPD) that could serve as diagnostic biomarkers or describe differential molecular mechanisms with potential therapeutic implications. METHODS: From a previously characterized cohort of ACO, COPD and asthmapatients, we selected a discovery group of 40 patients for miRNA expression profiling by means of microarray technology. Differential expression of miRNAs were validated by quantitative PCR in the complete cohort (n=274). RESULTS: Thirty differentially expressed miRNAs (eBAYES p<0.05, fold change ≥2) were found among the different groups of patients regarding COPDe: 19 COPD-vs-COPDe, 13 NSA-vs-COPDe, 11 SA-vs-COPDe. A characteristic down-regulated miRNA expression pattern was identified in COPDe patients. Differential expression of miR-619-5p and miR-4486 in COPDe patients were validated in the complete cohort (n=274). CONCLUSIONS: We postulate that COPDe patients show a characteristic expression profile of miRNAs distinctive from asthma and COPD. Also that SA and COPDe patients, which have been typically clustered in the ACO group, display distinct molecular events.
Authors: José A Cañas; José M Rodrigo-Muñoz; Beatriz Sastre; Marta Gil-Martinez; Natalia Redondo; Victoria Del Pozo Journal: Front Immunol Date: 2021-01-08 Impact factor: 7.561
Authors: Marc Miravitlles; Miguel Roman-Rodríguez; Xavier Ribera; John Ritz; José Luis Izquierdo Journal: Int J Chron Obstruct Pulmon Dis Date: 2022-01-25