2025/09/13 by Marta Molinero, Iván D. Benítez, Manel Perez‐Pons +24 · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Respiratory Support and Mechanisms #Extracellular vesicles in disease #MicroRNA in disease regulation
paper · doi:10.1016/j.omtn.2025.102714
openalex publication_date 2025/09/13 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
The application of microRNA (miRNA) profiling in respiratory biospecimens, particularly bronchial aspirate (BAS), remains underexplored. Here, we aimed to validate and refine miRNA quantification in BAS samples to establish its suitability for molecular phenotyping. This was a multicenter study including 288 COVID-19 patients on invasive mechanical ventilation. Respiratory biospecimens included BAS, tracheal aspirate, and bronchoalveolar lavage fluid samples. A predesigned miRNA panel was evaluated using RT-qPCR. Biomarker evaluation and functional assessment were subsequently conducted. An initial technical validation phase corroborated the reproducibility of miRNA profiling in BAS samples. Comparative analyses of miRNA expression profiles across respiratory samples revealed distinct miRNA patterns among biospecimens. In the biomarker analysis, two miRNA ratios, miR-34c-5p/miR-34a-5p and miR-34c-5p/miR-125b-5p, were inversely associated with intensive care unit (ICU) survival (hazard ratio [HR]: 0.18 and 0.17, respectively) during the discovery phase. Risk and survival analyses in the test phase confirmed the reproducibility of the miR-34c-5p/miR-34a-5p ratio (hazard ratio [HR] = 0.17). Functional analyses revealed the utility of miRNA profiling in BAS for identifying pathogenic pathways and developing therapeutic targets. Overall, these findings position miRNA profiling in BAS samples as a valuable approach for biomarker discovery, identification of pathophysiological mechanisms, and development of targeted pulmonary therapies.