Whole blood microRNA markers are associated with acute respiratory distress syndrome

Zhu, Zhaozhong; Liang, Liming; Zhang, Ruyang; Wei, Yongyue; Li, Su; Tejera, Paula; Guo, Yichen; Wang, Zhaoxi; Lu, Quan; Baccarelli, Andrea A.; Zhu, Xi; Bajwa, Ednan K.; Thompson, B. Taylor; Shi, Guo-Ping; Christiani, David C.

doi:10.1186/s40635-017-0155-0

Cited by 49 publications

(33 citation statements)

References 44 publications

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“…MiR-424 was shown to be a protective biomarker. Zhu concluded stating in addition to the miRNA, addition of the LIPS can improve the risk estimate of ARDS [69].…”

Section: Biomarkersmentioning

confidence: 99%

Biomarkers for Acute Respiratory Distress syndrome and prospects for personalised medicine

et al. 2019

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Acute lung injury (ALI) affects over 10% of patients hospitalised in critical care, with acute respiratory distress syndrome (ARDS) being the most severe form of ALI and having a mortality rate in the region of 40%. There has been slow but incremental progress in identification of biomarkers that contribute to the pathophysiology of ARDS, have utility in diagnosis and monitoring, and that are potential therapeutic targets (Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, Thompson T, Ware LB, Matthay MA, Lancet Respir Med 2014, 2:611–-620). However, a major issue is that ARDS is such a heterogeneous, multi-factorial, end-stage condition that the strategies for “lumping and splitting” are critical (Prescott HC, Calfee CS, Thompson BT, Angus DC, Liu VX, Am J Respir Crit Care Med 2016, 194:147–-155). Nevertheless, sequencing of the human genome, the availability of improved methods for analysis of transcription to mRNA (gene expression), and development of sensitive immunoassays has allowed the application of network biology to ARDS, with these biomarkers offering potential for personalised or precision medicine (Sweeney TE, Khatri P, Toward precision medicine Crit Care Med; 2017 45:934-939).Biomarker panels have potential applications in molecular phenotyping for identifying patients at risk of developing ARDS, diagnosis of ARDS, risk stratification and monitoring. Two subphenotypes of ARDS have been identified on the basis of blood biomarkers: hypo-inflammatory and hyper-inflammatory. The hyper-inflammatory subphenotype is associated with shock, metabolic acidosis and worst clinical outcomes. Biomarkers of particular interest have included interleukins (IL-6 and IL-8), interferon gamma (IFN-γ), surfactant proteins (SPD and SPB), von Willebrand factor antigen, angiopoietin 1/2 and plasminogen activator inhibitor-1 (PAI-1). In terms of gene expression (mRNA) in blood there have been found to be increases in neutrophil-related genes in sepsis-induced and influenza-induced ARDS, but whole blood expression does not give a robust diagnostic test for ARDS.Despite improvements in management of ARDS on the critical care unit, this complex disease continues to be a major life-threatening event. Clinical trials of β2-agonists, statins, surfactants and keratinocyte growth factor (KGF) have been disappointing. In addition, monoclonal antibodies (anti-TNF) and TNFR fusion protein have also been unconvincing. However, there have been major advances in methods of mechanical ventilation, a neuromuscular blocker (cisatracurium besilate) has shown some benefit, and stem cell therapy is being developed. In the future, by understanding the role of biomarkers in the pathophysiology of ARDS and lung injury, it is hoped that this will provide rational therapeutic targets and ultimately improve clinical care (Seymour CW, Gomez H, Chang CH, Clermont G, Kellum JA, Kennedy J, Yende S, Angus DC, Crit Care 2017, 21:257).

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“…MiR-424 was shown to be a protective biomarker. Zhu concluded stating in addition to the miRNA, addition of the LIPS can improve the risk estimate of ARDS [69].…”

Section: Biomarkersmentioning

confidence: 99%

Biomarkers for Acute Respiratory Distress syndrome and prospects for personalised medicine

et al. 2019

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“…miR-181 has been designated as a significant inflammatory response marker in whole blood analysis associated with sepsis-induced acute respiratory distress syndrome [ 72 ]. Decreased miR-181a expression reduced cell apoptosis of LPS-treated lung epithelial cells by targeting Bcl-2 [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Potential miRNAs, as Biomarkers for Sepsis and Associated Lung Injury: A Network-Based Approach

Ahmad

Ahmed

Hasan

et al. 2020

Genes

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Sepsis is a dysregulated immune response disease affecting millions worldwide. Delayed diagnosis, poor prognosis, and disease heterogeneity make its treatment ineffective. miRNAs are imposingly involved in personalized medicine such as therapeutics, due to their high sensitivity and accuracy. Our study aimed to reveal the biomarkers that may be involved in the dysregulated immune response in sepsis and lung injury using a computational approach and in vivo validation studies. A sepsis miRNA Gene Expression Omnibus (GEO) dataset based on the former analysis of blood samples was used to identify differentially expressed miRNAs (DEMs) and associated hub genes. Sepsis-associated genes from the Comparative Toxicogenomics Database (CTD) that overlapped with identified DEM targets were utilized for network construction. In total, 317 genes were found to be regulated by 10 DEMs (three upregulated, namely miR-4634, miR-4638-5p, and miR-4769-5p, and seven downregulated, namely miR-4299, miR-451a, miR181a-2-3p, miR-16-5p, miR-5704, miR-144-3p, and miR-1290). Overall hub genes (HIP1, GJC1, MDM4, IL6R, and ERC1) and for miR-16-5p (SYNRG, TNRC6B, and LAMTOR3) were identified based on centrality measures (degree, betweenness, and closeness). In vivo validation of miRNAs in lung tissue showed significantly downregulated expression of miR-16-5p corroborating with our computational findings, whereas expression of miR-181a-2-3p and miR-451a were found to be upregulated in contrast to the computational approach. In conclusion, the differential expression pattern of miRNAs and hub genes reported in this study may help to unravel many unexplored regulatory pathways, leading to the identification of critical molecular targets for increased prognosis, diagnosis, and drug efficacy in sepsis and associated organ injuries.

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“…The same group also reported analyses that compared microRNA expression in whole blood samples from patients with ARDS and critically ill at-risk control patients (Zhu et al 2017). They revealed that the levels of miR-181a or miR-92a were positively correlated with a risk for the development of ARDS, whereas miR-424 was negatively correlated with a risk for ARDS.…”

Section: The Changes and The Roles Of Micrornas In Ardsmentioning

confidence: 99%

The Roles of MicroRNAs and Extracellular Vesicles in the Pathogeneses of Idiopathic Pulmonary Fibrosis and Acute Respiratory Distress Syndrome

Yamada

2020

Tohoku J. Exp. Med.

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The lungs are the organs that work for gas exchange. The basic structure of the lungs is an alveolus, which consists of various types of parenchymal cells and bone marrow-derived cells. Therefore, because the lungs consist of various types of cells with various functions, communication among the different types of the cells should play important roles for the homeostasis and response to disease pathogens. In the past decades, researchers have focused on cytokines or adhesion molecules to reveal the intercellular communication for understanding the homeostasis and pathogenesis in the lungs. Recent investigations have revealed that an extracellular vesicle can move among cells for transferring substances including microRNAs in the vesicles as an intercellular messenger. MicroRNAs and extracellular vesicles are therefore attracting increasing attention from both translational and clinical researchers because these emerging intercellular communication tools seem to be useful for further understanding of the disease pathogenesis as well as the biomarkers for diagnosis and prognosis of the diseases including cancer and inflammatory diseases. This review article is an attempt to review studies about microRNAs and extracellular vesicles in terms of their roles in normal conditions and refractory diseases of the lungs such as idiopathic pulmonary fibrosis and acute respiratory distress syndrome including our recent study about pulmonary microvascular endothelial microparticles particles as the biomarker for diagnosis and prognosis of acute respiratory distress syndrome. This review also addresses the possibility of microRNAs and extracellular vesicles as new clinical tools for the diagnosis or treatment for these refractory respiratory diseases.

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Whole blood microRNA markers are associated with acute respiratory distress syndrome

Cited by 49 publications

References 44 publications

Biomarkers for Acute Respiratory Distress syndrome and prospects for personalised medicine

Biomarkers for Acute Respiratory Distress syndrome and prospects for personalised medicine

Identification and Validation of Potential miRNAs, as Biomarkers for Sepsis and Associated Lung Injury: A Network-Based Approach

The Roles of MicroRNAs and Extracellular Vesicles in the Pathogeneses of Idiopathic Pulmonary Fibrosis and Acute Respiratory Distress Syndrome

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