Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases

PLoS One. 2015 Sep 9;10(9):e0137522. doi: 10.1371/journal.pone.0137522. eCollection 2015.

Abstract

Objective: Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested.

Methods: We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and osteoarthritis. Then we detected overlaps of differentially expressed genes across datasets and performed a meta-analysis aiming at identifying common differentially expressed genes that discriminate between pathological cases and normal controls. To further gain insights into the functions of the identified common differentially expressed genes, we conducted gene ontology enrichment analysis and protein-protein interaction analysis.

Results: We identified a total of eight differentially expressed genes (TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, PRF1), each associated with at least 3 of the 4 studied rheumatic diseases. Meta-analysis warranted the significance of the eight genes and highlighted the general significance of four genes (CX3CR1, LY96, TLR5, and PRF1). Protein-protein interaction and gene ontology enrichment analyses indicated that the eight genes interact with each other to exert functions related to immune response and immune regulation.

Conclusion: The findings support that there exist common factors underlying rheumatic diseases. For rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and osteoarthritis diseases, those common factors include TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, and PRF1. In-depth studies on these common factors may provide keys to understanding the pathogenesis and developing intervention strategies for rheumatic diseases.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / pathology
  • Biomarkers
  • Gene Expression Regulation
  • Humans
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / pathology
  • Osteoarthritis / genetics*
  • Osteoarthritis / pathology
  • Protein Biosynthesis / genetics
  • Protein Interaction Maps / genetics
  • Risk Factors
  • Spondylitis, Ankylosing / genetics*
  • Spondylitis, Ankylosing / pathology
  • Transcriptome*

Substances

  • Biomarkers

Grants and funding

The study was supported by the national Natural Science Foundation of China http://www.nsfc.gov.cn/ (81373010, 81473046, 31401079, 81401343, 31271336, and 31071097), the Natural Science Foundation of Jiangsu Province http://www.jstd.gov.cn/ (BK20130300), the Startup Fund from Soochow University http://www.suda.edu.cn/ (Q413900112, Q413900712). SFL received the funding. The funders had role in study design, data collection and analysis, decision to publish, and preparation of the manuscript.