scholarly journals Bioinformatics analysis of the potential biomarkers for acute respiratory distress syndrome

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Lin Liao ◽  
Pinhu Liao
Keyword(s):  
Gene Expression ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Potential Biomarker ◽  
Potential Biomarkers

Abstract Background: Acute respiratory distress syndrome (ARDS) is caused by uncontrolled inflammation, and the activation of alveolar macrophages (AM) is involved in pathophysiologic procedures. The present study aimed to identify key AM genes and pathways and try to provide potential targets for prognosis and early intervention in ARDS. Methods: The mRNA expression profile of GSE89953 was obtained from the Gene Expression Omnibus database. The LIMMA package in R software was used to identify differentially expressed genes (DEGs), and the clusterProfiler package was used for functional enrichment and pathway analyses. A protein–protein interaction network of DEGs was constructed to identify hub genes via the STRING database and Cytoscape software. Hub gene expression was validated using differentially expressed proteins (DEPs) obtained from the ProteomeXchange datasets to screen potential biomarkers. Results: A total of 166 DEGs (101 up-regulated and 65 down-regulated) were identified. The up-regulated DEGs were mainly enriched in regulation of the ERK1 and ERK2 cascade, response to interferon-gamma, cell chemotaxis, and migration in biological processes. In the KEGG pathway analysis, up-regulated DEGs were mainly involved in rheumatoid arthritis, cytokine–cytokine receptor interactions, phagosome, and the chemokine signaling pathway. The 12 hub genes identified included GZMA, MPO, PRF1, CXCL8, ELANE, GZMB, SELL, APOE, SPP1, JUN, CD247, and CCL2. Conclusion: SPP1 was consistently differentially expressed in both DEGs and DEPs. SPP1 could be a potential biomarker for ARDS.

Alveolar MMP28 is Associated With Clinical Outcomes and Measures of Lung Injury in Acute Respiratory Distress Syndrome

2020 ◽  
Author(s):  
Eric Morrell ◽  
Carmen Mikacenic ◽  
Ke-Qin Gong ◽  
Susanna Kosamo ◽  
Renee D. Stapleton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Clinical Outcomes ◽  
Peripheral Blood ◽  
Distress Syndrome ◽  
Lavage Fluid ◽  
Peripheral Blood Monocyte ◽  
Omega 3

Abstract Background Excessive inflammation leading to increased alveolar-capillary barrier permeability remains the pathogenic model for acute respiratory distress syndrome (ARDS). Alveolar macrophage (AM) polarization has been shown to modify the activity of various matrix metalloproteinases (MMPs) that have downstream effects on key ARDS cytokines/chemokines, however the relationship between AMs, MMP28 (the newest member of the MMP family), and ARDS clinical outcomes is unknown.Methods We analyzed bronchoalveolar lavage fluid (BALF) and peripheral blood from subjects previously enrolled in a phase-II trial of omega-3 fatty acids for the treatment of ARDS ( n = 76). In a subset of these patients ( n = 25), we tested for assocations between AM- and peripheral blood monocyte (PBM)-specific MMP28 gene expression and clincal outcomes [ventilator-free days (VFDs), P a O 2 /F i O 2 ratio (P/F ratio), and sequential organ failure assessment score (SOFA)]. We tested for assocations between soluble BALF or plasma MMP28 concentrations and ARDS clinical outcomes and inflammatory mediator concentrations in the entire cohort.Results Increased AM MMP28 gene expression was significantly associated with worse VFDs and P/F ratio ( p < 0.05). Higher BALF MMP28 concentrations were associated with worse P/F, but not VFDs. Increased BALF MMP28 concentrations were associated with increased % neutrophils as well as BALF total protein, IL-6, IL-17A, and MCP-1 concentrations (all p < 0.05). Plasma MMP28 concentrations were not associated with any clinical outcome. Increased PBM MMP28 gene expression was associated with worse P/F ratio but not VFDs.Conclusions Higher AM MMP28 gene expression and BALF MMP28 concentrations are associated with poor clinical outcomes and with increased alveolar inflammatory mediators in patients with ARDS.

scholarly journals Alveolar CCN1 is associated with mechanical stretch and acute respiratory distress syndrome severity

2020 ◽  
Vol 319 (5) ◽  
pp. L825-L832
Author(s):  
Eric D. Morrell ◽  
Serge Grazioli ◽  
Chi Hung ◽  
Osamu Kajikawa ◽  
Susanna Kosamo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Mechanical Stretch ◽  
Mechanically Ventilated ◽  
Alveolar Epithelial ◽  
Protein Levels

The cellular communication network factor 1 (CCN1) is a matricellular protein that can modulate multiple tissue responses, including inflammation and repair. We have previously shown that adenoviral overexpression of Ccn1 is sufficient to cause acute lung injury in mice. We hypothesized that CCN1 is present in the airspaces of lungs during the acute phase of lung injury, and higher concentrations are associated with acute respiratory distress syndrome (ARDS) severity. We tested this hypothesis by measuring 1) CCN1 in bronchoalveolar lavage fluid (BALF) and lung homogenates from mice subjected to ventilation-induced lung injury (VILI), 2) Ccn1 gene expression and protein levels in MLE-12 cells (alveolar epithelial cell line) subjected to mechanical stretch, and 3) CCN1 in BALF from mechanically ventilated humans with and without ARDS. BALF CCN1 concentrations and whole lung CCN1 protein levels were significantly increased in mice with VILI ( n = 6) versus noninjured controls ( n = 6). Ccn1 gene expression and CCN1 protein levels were increased in MLE-12 cells cultured under stretch conditions. Subjects with ARDS ( n = 77) had higher BALF CCN1 levels compared with mechanically ventilated subjects without ARDS ( n = 45) ( P < 0.05). In subjects with ARDS, BALF CCN1 concentrations were associated with higher total protein, sRAGE, and worse [Formula: see text]/[Formula: see text] ratios (all P < 0.05). CCN1 is present in the lungs of mice and humans during the acute inflammatory phase of lung injury, and concentrations are higher in patients with increased markers of severity. Alveolar epithelial cells may be an important source of CCN1 under mechanical stretch conditions.

scholarly journals Bacteria-Specific Neutrophil Dysfunction Associated with Interferon-Stimulated Gene Expression in the Acute Respiratory Distress Syndrome

PLoS ONE ◽  
2011 ◽  
Vol 6 (7) ◽  
pp. e21958 ◽  
Author(s):  
Kenneth C. Malcolm ◽  
Jennifer E. Kret ◽  
Robert L. Young ◽  
Katie R. Poch ◽  
Silvia M. Caceres ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Neutrophil Dysfunction

scholarly journals Assessment of Alveolar Macrophage Dysfunction Using an in vitro Model of Acute Respiratory Distress Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Rahul Y. Mahida ◽  
Aaron Scott ◽  
Dhruv Parekh ◽  
Sebastian T. Lugg ◽  
Kylie B. R. Belchamber ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Alveolar Macrophage ◽  
Distress Syndrome ◽  
Lung Resection ◽  
Macrophage Dysfunction

Background: Impaired alveolar macrophage (AM) efferocytosis may contribute to acute respiratory distress syndrome (ARDS) pathogenesis; however, studies are limited by the difficulty in obtaining primary AMs from patients with ARDS. Our objective was to determine whether an in vitro model of ARDS can recapitulate the same AM functional defect observed in vivo and be used to further investigate pathophysiological mechanisms.Methods: AMs were isolated from the lung tissue of patients undergoing lobectomy and then treated with pooled bronchoalveolar lavage (BAL) fluid previously collected from patients with ARDS. AM phenotype and effector functions (efferocytosis and phagocytosis) were assessed by flow cytometry. Rac1 gene expression was assessed using quantitative real-time PCR.Results: ARDS BAL treatment of AMs decreased efferocytosis (p = 0.0006) and Rac1 gene expression (p = 0.016); however, bacterial phagocytosis was preserved. Expression of AM efferocytosis receptors MerTK (p = 0.015) and CD206 (p = 0.006) increased, whereas expression of the antiefferocytosis receptor SIRPα decreased following ARDS BAL treatment (p = 0.036). Rho-associated kinase (ROCK) inhibition partially restored AM efferocytosis in an in vitro model of ARDS (p = 0.009).Conclusions: Treatment of lung resection tissue AMs with ARDS BAL fluid induces impairment in efferocytosis similar to that observed in patients with ARDS. However, AM phagocytosis is preserved following ARDS BAL treatment. This specific impairment in AM efferocytosis can be partially restored by inhibition of ROCK. This in vitro model of ARDS is a useful tool to investigate the mechanisms by which the inflammatory alveolar microenvironment of ARDS induces AM dysfunction.

scholarly journals Identification of potential biomarkers with colorectal cancer based on bioinformatics analysis and machine learning

2021 ◽  
Vol 18 (6) ◽  
pp. 8997-9015
Author(s):  
Ahmed Hammad ◽  
◽  
Mohamed Elshaer ◽  
Xiuwen Tang ◽  
◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Machine Learning ◽  
Roc Curve ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Ppi Network ◽  
Hub Genes ◽  
Survival Analyses ◽  
Potential Biomarkers

<abstract> <p>Colorectal cancer (CRC) is one of the most common malignancies worldwide. Biomarker discovery is critical to improve CRC diagnosis, however, machine learning offers a new platform to study the etiology of CRC for this purpose. Therefore, the current study aimed to perform an integrated bioinformatics and machine learning analyses to explore novel biomarkers for CRC prognosis. In this study, we acquired gene expression microarray data from Gene Expression Omnibus (GEO) database. The microarray expressions GSE103512 dataset was downloaded and integrated. Subsequently, differentially expressed genes (DEGs) were identified and functionally analyzed via Gene Ontology (GO) and Kyoto Enrichment of Genes and Genomes (KEGG). Furthermore, protein protein interaction (PPI) network analysis was conducted using the STRING database and Cytoscape software to identify hub genes; however, the hub genes were subjected to Support Vector Machine (SVM), Receiver operating characteristic curve (ROC) and survival analyses to explore their diagnostic values. Meanwhile, TCGA transcriptomics data in Gene Expression Profiling Interactive Analysis (GEPIA) database and the pathology data presented by in the human protein atlas (HPA) database were used to verify our transcriptomic analyses. A total of 105 DEGs were identified in this study. Functional enrichment analysis showed that these genes were significantly enriched in biological processes related to cancer progression. Thereafter, PPI network explored a total of 10 significant hub genes. The ROC curve was used to predict the potential application of biomarkers in CRC diagnosis, with an area under ROC curve (AUC) of these genes exceeding 0.92 suggesting that this risk classifier can discriminate between CRC patients and normal controls. Moreover, the prognostic values of these hub genes were confirmed by survival analyses using different CRC patient cohorts. Our results demonstrated that these 10 differentially expressed hub genes could be used as potential biomarkers for CRC diagnosis.</p> </abstract>

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