Abstract

BackgroundTo identify critical genes and biological pathways in acute lung injury (ALI), a comparative analysis of gene expression profiles of patients with ALI + sepsis compared with patients with sepsis alone were performed with bioinformatic tools.MethodsGSE10474 was downloaded from Gene Expression Omnibus, including a collective of 13 whole blood samples with ALI + sepsis and 21 whole blood samples with sepsis alone. After pre-treatment with robust multichip averaging (RMA) method, differential analysis was conducted using simpleaffy package based upon t-test and fold change. Hierarchical clustering was also performed using function hclust from package stats. Beisides, functional enrichment analysis was conducted using iGepros. Moreover, the gene regulatory network was constructed with information from Kyoto Encyclopedia of Genes and Genomes (KEGG) and then visualized by Cytoscape.ResultsA total of 128 differentially expressed genes (DEGs) were identified, including 47 up- and 81 down-regulated genes. The significantly enriched functions included negative regulation of cell proliferation, regulation of response to stimulus and cellular component morphogenesis. A total of 27 DEGs were significantly enriched in 16 KEGG pathways, such as protein digestion and absorption, fatty acid metabolism, amoebiasis, etc. Furthermore, the regulatory network of these 27 DEGs was constructed, which involved several key genes, including protein tyrosine kinase 2 (PTK2), v-src avian sarcoma (SRC) and Caveolin 2 (CAV2).ConclusionPTK2, SRC and CAV2 may be potential markers for diagnosis and treatment of ALI.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5865162912987143

Highlights

  • To identify critical genes and biological pathways in acute lung injury (ALI), a comparative analysis of gene expression profiles of patients with ALI + sepsis compared with patients with sepsis alone were performed with bioinformatic tools

  • Gene regulatory network construction A total of 27 differentially expressed genes (DEGs) were significantly enriched in 16 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways

  • Expressed genes According to the criteria, a total of 128 DEGs were identified in patients with ALI + sepsis compared with patients with sepsis alone, including 47 up-regulated genes and 81 down-regulated genes

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Summary

Introduction

To identify critical genes and biological pathways in acute lung injury (ALI), a comparative analysis of gene expression profiles of patients with ALI + sepsis compared with patients with sepsis alone were performed with bioinformatic tools. Acute lung injury (ALI), called acute respiratory distress syndrome (ARDS), is a systemic inflammatory response syndrome characterized by refractory hypoxemia and respiratory distress [1]. It can be caused by all kinds of pathogenic factors inside and outside the lungs (such as serious infection, aspiration, sepsis, trauma and shock), principally sepsis [1,2,3]. Gene expression profiles analysis has been conducted, microarray technology enables a global investigation of gene expression and promotes identification of biomarkers of potential diagnostic and prognostic significance [11,12,13] It provides insights on the molecular mechanisms underlying the ALI [14,15]

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