Identification of potential peripheral blood diagnostic biomarkers for patients with juvenile idiopathic arthritis by bioinformatics analysis

Abstract

Juvenile idiopathic arthritis (JIA) is common childhood rheumatic disease harming children health. However, there is still lack of effective biomarkers for diagnosis JIA at early onset. We aim to construct a classification model to predict JIA disease. The peripheral blood gene expression profile data of JIA were downloaded from GEO database. We compared and analyzed differentially expressed genes (DEGs) between different JIA samples through Pearson's correlation coefficient method and unsupervised clustering analysis. Diagnostic model were constructed based on the deviation pathway through bioinformatics method. Eighteen specific correlated DEGs were obtained, but the correlations altered in different disease states. Although most JIA and control samples were clustered by unsupervised clustering analysis, respectively, a few JIA samples could not be clustered well. Four co-expression networks were next constructed with gene connections dynamically altered under variable conditions. Eight signaling pathways were significantly enriched including B/T cell receptor, ErbB and MAPK signaling pathways. The deviation scores of pathways were calculated. Applying these eight signaling pathways as feature to construct a classification model could predict JIA disease with high accuracies. Our data provide some light into pathogenic mechanism of JIA, the specific gene sets and the related signaling pathways may be potential biomarkers for diagnosis or therapeutic targets of JIA.

Interleukin-6 in juvenile idiopathic arthritis

“…A positive feedback loop via the epiregulin-ErbB1 pathway [17] is known to act as an IL-6 amplifier in RA joints [18]. Given that the ErbB-signaling pathway is activated in all types of JIA [19] as well as in RA, an amplified IL-6 system is expected to be locally involved in the pathogenesis.…”

Proteomic profiling of extracellular vesicles in synovial fluid and plasma from Oligoarticular Juvenile Idiopathic Arthritis patients reveals novel immunopathogenic biomarkers

“…To date, only a few molecular, immune, and clinical markers have, in fact, been proposed ( 9 , 14 – 17 ). Therefore, a great deal of efforts is currently being expended in the search of new biomarkers readily measurable in patient-derived material at an early stage of the disease and in a minimally invasive way ( 12 , 18 , 19 ). A deeper understanding of the molecular regulatory mechanisms underlying OJIA pathophysiology is critical for the discovery of candidate biomarkers and potential novel therapeutic targets.…”

Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy

“…43 This became a crucial step that allows numerous alternative and/or overlapping ways to remake normal cytosine residue either autonomously or in a DNA replication-dependent manner thereby causing final removal of the methyl mark. 25,[44][45][46][47][48][49] Active DNA demethylation can occur via direct removal of a methyl group independently of DNA replication. The underlying various mechanisms include enzymatic exclusion of the methyl group, base excision repair, deamination followed by mismatch repair, nucleotide excision repair and oxidative demethylation.…”

“… 43 This became a crucial step that allows numerous alternative and/or overlapping ways to remake normal cytosine residue either autonomously or in a DNA replication-dependent manner thereby causing final removal of the methyl mark. 25 , 44 - 49 …”