Integrative analyses reveal biological pathways and key genes in psoriasis

Br J Dermatol. 2017 Nov;177(5):1349-1357. doi: 10.1111/bjd.15682. Epub 2017 Oct 25.

Abstract

Background: Psoriasis is a complex disease influenced by both genetic and environmental factors with abnormal gene expression in lesional skin. However, no studies are available on genome-scale gene expression of psoriatic lesions in the Chinese population. In addition, systematic studies on the biological pathways, pathogenicity and interaction networks of psoriasis-related genes with abnormal expression profiles require further investigation.

Objectives: To further explore the associated pathways in psoriasis by functional analysis and to identify the key genes by gene pathogenicity analysis.

Methods: We performed RNA sequencing on 60 skin biopsy samples from patients with psoriasis and healthy controls to identify the primary differentially expressed genes in psoriatic lesional skin. We retrieved all reported psoriasis-associated genes and performed integrative analyses covering gene expression profiling, pathway analysis, gene pathogenicities and protein-protein interaction networks.

Results: We found that internal and external stimuli may activate immunoinflammatory responses to promote the development of psoriasis. Pathways associated with infectious diseases and cancers were identified by functional and pathway analyses. The gene pathogenicity analysis revealed five key genes in psoriasis: PPARD, GATA3, TIMP3, WNT5A and PTTG1.

Conclusions: Our analyses showed that genes contributed to the pathogenesis of psoriasis by activating risk pathways with components abnormality in expression. We identified five potentially pathogenic genes for psoriasis that may serve as important biomarkers for the diagnosis and treatment.

MeSH terms

  • Adult
  • Case-Control Studies
  • Female
  • GATA3 Transcription Factor / genetics
  • Gene Expression Profiling
  • Genetic Markers / genetics
  • Humans
  • Male
  • PPAR delta / genetics
  • Proteins / genetics*
  • Psoriasis / genetics*
  • Securin / genetics
  • Sequence Analysis, RNA
  • Signal Transduction / genetics
  • Tissue Inhibitor of Metalloproteinase-3 / genetics
  • Wnt-5a Protein / genetics

Substances

  • GATA3 Transcription Factor
  • Genetic Markers
  • PPAR delta
  • Proteins
  • Securin
  • Tissue Inhibitor of Metalloproteinase-3
  • WNT5A protein, human
  • Wnt-5a Protein
  • pituitary tumor-transforming protein 1, human