ArticleArthritis research & therapy2017
Limited cutaneous systemic sclerosis skin demonstrates distinct molecular subsets separated by a cardiovascular development gene expression signature.
Article in Arthritis research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Current Concepts on the Pathogenesis of Systemic Sclerosis.Clinical reviews in allergy & immunology · 2023Review
- Alterations of the Primary Cilia Gene SPAG17 and SOX9 Locus Noncoding RNAs Identified by RNA-Sequencing Analysis in Patients With Systemic Sclerosis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Differential DNA Methylation Landscape in Skin Fibroblasts from African Americans with Systemic Sclerosis.Genes · 2021Article
- Molecular "omic" signatures in systemic sclerosis.European journal of rheumatology · 2020Review
- Shared and distinct mechanisms of fibrosis.Nature reviews. Rheumatology · 2019Review
- Screening and identification of biomarkers for systemic sclerosis via microarray technology.International journal of molecular medicine · 2019Article
- Identification of Key Genes and Pathways in Female Lung Cancer Patients Who Never Smoked by a Bioinformatics Analysis.Journal of Cancer · 2019Article
- Existing and novel biomarkers for precision medicine in systemic sclerosis.Nature reviews. Rheumatology · 2018Review
- Integrated analysis of hepatic mRNA and miRNA profiles identified molecular networks and potential biomarkers of NAFLD.Scientific reports · 2018Article
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundSystemic sclerosis (SSc; scleroderma) is an uncommon autoimmune rheumatic disease characterised by autoimmunity, vasculopathy and fibrosis. Gene expression profiling distinguishes scleroderma from normal skin, and can detect different subsets of disease, with potential to identify prognostic biomarkers of organ involvement or response to therapy. We have performed gene expression profiling in skin samples from patients with limited cutaneous SSc (lcSSc).
methodsTotal RNA was extracted from clinically uninvolved skin biopsies of 15 patients with lcSSc and 8 healthy controls (HC). Gene expression profiling was performed on a DNA oligonucleotide microarray chip. Differentially expressed genes (DEG) were identified using significance analysis of microarrays (SAM). Functional enrichment analysis of gene signatures was done via g:Profiler.
resultsThere were 218 DEG between lcSSc and HC samples (false discovery rate <10%): 181/218 DEG were upregulated in lcSSc samples. Hierarchical clustering of DEG suggested the presence of two separate groups of lcSSc samples: "limited 1" and "limited 2". The limited-1 group (13 samples, 10 unique patients) showed upregulation of genes involved in cell adhesion, cardiovascular system (CVS) development, extracellular matrix and immune and inflammatory response. The CVS development signature was of particular interest as its genes showed very strong enrichment in response to wounding, response to transforming growth factor (TGF)-β and kinase cascade. Neither limited-2 samples (six samples, five unique patients) nor HC samples showed functional enrichment. There were no significant differences in demographic or clinical parameters between these two groups. These results were confirmed using a second independent cohort.
conclusionsOur study suggests the presence of molecular subsets in lcSSc based on gene expression profiling of biopsies from uninvolved skin. This may reflect important differences in pathogenesis within these patient groups. We identify differential expression of a subset of genes that relate to CVS and are enriched in fibrotic signalling. This may shed light on mechanisms of vascular disease in SSc. The enrichment in profibrotic profile suggests that dysregulated gene expression may contribute to vasculopathy and fibrosis in different disease subsets.
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