Identification of a Circulating miRNA Signature to Stratify Acute Respiratory Distress Syndrome Patients.

Gennaro Martucci,Pier Giulio Conaldi,Fabio Tuzzolino,Chiara Vitiello,Claudia Carcione,Antonio Arcadipane,Vitale Miceli,Giovanna Occhipinti,Roberto Lorusso,Eleonora Bonicolini,Giovanna Panarello

doi:10.3390/jpm11010015

Abstract

There is a need to improve acute respiratory distress syndrome (ARDS) diagnosis and management, particularly with extracorporeal membrane oxygenation (ECMO), and different biomarkers have been tested to implement a precision-focused approach. We included ARDS patients on veno-venous (V-V) ECMO in a prospective observational pilot study. Blood samples were obtained before cannulation, and screened for the expression of 754 circulating microRNA (miRNAs) using high-throughput qPCR and hierarchical cluster analysis. The miRNet database was used to predict target genes of deregulated miRNAs, and the DIANA tool was used to identify significant enrichment pathways. A hierarchical cluster of 229 miRNAs (identified after quality control screening) produced a clear separation of 11 patients into two groups: considering the baseline SAPS II, SOFA, and RESP score cluster A (n = 6) showed higher severity compared to cluster B (n = 5); p values < 0.05. After analysis of differentially expressed miRNAs between the two clusters, 95 deregulated miRNAs were identified, and reduced to 13 by in silico analysis. These miRNAs target genes implicated in tissue remodeling, immune system, and blood coagulation pathways. The blood levels of 13 miRNAs are altered in severe ARDS. Further investigations will have to match miRNA results with inflammatory biomarkers and clinical data.

Highlights

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung disease characterized by the loss of lung endothelial barrier integrity, and invasion of alveoli by fluids, proteins, and inflammatory cells [1]
From July 2018 to March 2019, 13 patients were supported by V-V extracorporeal membrane oxygenation (ECMO) for ARDS at our institute
We found a select pattern of miRNA expression capable of separating patients into two clusters that differ in baseline ARDS severity, and between these clusters, we performed an analysis of the differentially expressed miRNAs

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung disease characterized by the loss of lung endothelial barrier integrity, and invasion of alveoli by fluids, proteins, and inflammatory cells [1]. ARDS is characterized by persistent injury stimuli and the failure of lung tissue repair that evolves into chronic lung repair, resulting in marked changes in lung structure and function [3]. In this clinical picture, the Berlin definition [4] has helped to define the syndrome, and the subsequent LUNGSAFE study described its application worldwide [5]. The appearance of COVID-19 has cast into question the presence of a “classical” ARDS and a “new” form, with the same clinical definition but different pathophysiology [6,7,8]

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