Screening for key genes associated with atopic dermatitis with DNA microarrays

Mol Med Rep. 2014 Mar;9(3):1049-55. doi: 10.3892/mmr.2014.1908. Epub 2014 Jan 21.

Abstract

The aim of the present study was to identify key genes associated with atopic dermatitis (AD) using microarray data and bioinformatic analyses. The dataset GSE6012, downloaded from the Gene Expression Omnibus (GEO) database, contains gene expression data from 10 AD skin samples and 10 healthy skin samples. Following data preprocessing, differentially expressed genes (DEGs) were identified using the limma package of the R project. Interaction networks were constructed comprising DEGs that showed a degree of node of >3, >5 and >10, using the Osprey software. Functional enrichment and pathway enrichment analysis of the network comprising all DEGs and of the network comprising DEGs with a high degree of node, were performed with the DAVID and WebGestalt toolkits, respectively. A total of 337 DEGs were identified. The functional enrichment analysis revealed that the list of DEGs was significantly enriched for proteins related to epidermis development (P=2.95E-07), including loricrin (LOR), keratin 17 (KRT17), small proline-rich repeat proteins (SPRRs) and involucrin (IVL). The chemokine signaling pathway was the most significantly enriched pathway (P=0.0490978) in the network of all DEGs and in the network consisting of high degree‑node DEGs (>10), which comprised the genes coding for chemokine receptor 7 (CCR7), chemokine ligand (CCL19), signal transducer and activator of transcription 1 (STAT1), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1). In conclusion, the list of AD-associated proteins identified in this study, including LOR, KRT17, SPRRs, IVL, CCR7, CCL19, PIK3R1 and STAT1 may prove useful for the development of methods to treat AD. From these proteins, PIK3R1 and KRT17 are novel and promising targets for AD therapy.

MeSH terms

  • Chemokine CCL19 / genetics
  • Class Ia Phosphatidylinositol 3-Kinase
  • Computational Biology
  • Cornified Envelope Proline-Rich Proteins / genetics
  • Databases, Genetic
  • Dermatitis, Atopic / genetics*
  • Dermatitis, Atopic / metabolism
  • Dermatitis, Atopic / pathology
  • Gene Regulatory Networks
  • Humans
  • Keratin-17 / genetics
  • Membrane Proteins / genetics
  • Oligonucleotide Array Sequence Analysis*
  • Phosphatidylinositol 3-Kinases / genetics
  • Protein Precursors / genetics
  • Receptors, CCR7 / genetics
  • STAT1 Transcription Factor / genetics
  • Signal Transduction / genetics
  • Software

Substances

  • CCR7 protein, human
  • Chemokine CCL19
  • Cornified Envelope Proline-Rich Proteins
  • Keratin-17
  • Membrane Proteins
  • Protein Precursors
  • Receptors, CCR7
  • STAT1 Transcription Factor
  • loricrin
  • involucrin
  • PIK3R1 protein, human
  • Class Ia Phosphatidylinositol 3-Kinase