Specific microRNA Profile Associated with Inflammation and Lipid Metabolism for Stratifying Allergic Asthma Severity
The mechanisms underlying severe allergic asthma are complex and unknown, meaning it is a challenge to provide the most appropriate treatment. This study aimed to identify novel biomarkers for stratifying allergic asthmatic patients according to severity, and to uncover the biological mechanisms that lead to the development of the severe uncontrolled phenotype. By using miRNA PCR panels, we analyzed the expression of 752 miRNAs in serum samples from control subjects (<i>n</i> = 15) and mild (<i>n</i> = 11) and severe uncontrolled (<i>n</i> = 10) allergic asthmatic patients. We identified 40 differentially expressed miRNAs between severe uncontrolled and mild allergic asthmatic patients. Functional enrichment analysis revealed signatures related to inflammation, angiogenesis, lipid metabolism and mRNA regulation. A random forest classifier trained with DE miRNAs achieved a high accuracy of 97% for severe uncontrolled patient stratification. Validation of the identified biomarkers was performed on a subset of allergic asthmatic patients from the CAMP cohort at Brigham and Women's Hospital, Harvard Medical School. Four of these miRNAs (hsa-miR-99b-5p, hsa-miR-451a, hsa-miR-326 and hsa-miR-505-3p) were validated, pointing towards their potential as biomarkers for stratifying allergic asthmatic patients by severity and providing insights into severe uncontrolled asthma molecular pathways.
Authors
- Heleia González Cuervo (ORCID: https://orcid.org/0009-0001-6809-2410)
- Michael J. McGeachie (ORCID: https://orcid.org/0000-0001-5566-2712)
- María Isabel Delgado Dolset (ORCID: https://orcid.org/0000-0001-7924-5454)
- Rinku Sharma (ORCID: https://orcid.org/0000-0003-3036-2080)
- Leticia Mera‐Berriatua
- Domingo Barber (ORCID: https://orcid.org/0000-0002-5488-5700)
- Carmela Pablo‐Torres (ORCID: https://orcid.org/0000-0003-2861-5763)
- Teresa Carrillo (ORCID: https://orcid.org/0000-0002-3047-8908)
- Alvin T. Kho (ORCID: https://orcid.org/0000-0002-9887-312X)
- María Marta Escribese (ORCID: https://orcid.org/0000-0001-5057-5150)
- Kelan G. Tantisira (ORCID: https://orcid.org/0000-0003-2950-3384)
- Elena Izquierdo (ORCID: https://orcid.org/0000-0002-3355-2798)
- Andrea Escolar‐Peña (ORCID: https://orcid.org/0009-0008-8197-6107)
- R. R. Rios (ORCID: https://orcid.org/0000-0002-8910-867X)
- María del Pilar Cuesta Apausa
- Carlos Tarin (ORCID: https://orcid.org/0000-0003-4385-9467)
Institutions
- Universidad San Pablo CEU (ES)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- University of Cologne (DE)
- University of California San Diego (US)
- Rady Children's Hospital-San Diego (US)
- Düsseldorf University Hospital (DE)
- Hospital Universitario de Gran Canaria Doctor Negrín (ES)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- University Hospital Cologne (DE)
- Heinrich Heine University Düsseldorf (DE)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2024-08-30
- DOI
- https://doi.org/10.3390/ijms25179425
- Citations
- 1
- Primary Topic
- MicroRNA in disease regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.29
Funders
- Fundación Mutua Madrileña
- Instituto de Salud Carlos III
- European Regional Development Fund