Distinct gene network in skin lesion of patients with diffuse cutaneous systemic sclerosis
- PDF / 502,941 Bytes
- 2 Pages / 595.276 x 790.866 pts Page_size
- 105 Downloads / 175 Views
LETTERS OF BIOMEDICAL AND CLINICAL RESEARCH
Distinct gene network in skin lesion of patients with diffuse cutaneous systemic sclerosis Jun Inamo 1 Received: 9 May 2020 / Revised: 9 May 2020 / Accepted: 15 June 2020 # International League of Associations for Rheumatology (ILAR) 2020
Diffuse cutaneous systemic sclerosis (dcSSc) is an autoimmune disease characterized by fibrosis and high morbidity and mortality. Progression of skin lesion is associated with subsequent progression of visceral organ lesion and high mortality, suggesting critical disorder may be shared among various lesions [1]. Thus, skin biopsy has been conducted to explore the key molecule in the pathogenesis of dcSSc in situ. Recent studies revealed that fibro-inflammatory pathways were dysregulated in skin lesion by transcriptome profiling [2, 3]. However, these results were based on expression levels of single molecules. To understand the pathogenesis of dcSSc correctly, remaining challenges include how to best identify genes of interest from large datasets. Weighted gene co-expression network analysis (WGCNA) is a system biology method and widely used for finding gene clusters (modules) of highly correlated genes by summarizing such clusters using the module eigengene [4]. Correlation networks facilitate network-based gene screening that can be used to identify candidate biomarkers or therapeutic targets. Here, to identify distinct gene network in skin lesion of dcSSc, consensus network analysis was applied to the expression datasets of patients with dcSSc and healthy controls (HC). Gene expression dataset using RNA sequencing of skin biopsy from 56 patients in the Prospective Registry for Early Systemic Sclerosis (PRESS) cohort (mean disease duration 1.3 years) and Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10067-020-05245-7) contains supplementary material, which is available to authorized users. * Jun Inamo [email protected] 1
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
33 matched HC was leveraged [3]. For quality control, top 10,000 genes with high intensity variance among subjects were processed further analysis. Functional enrichment and pathway analysis were conducted using Gene Ontology terms, Kyoto Encyclopedia of Genes and Genomes pathway, Hall mark gene sets, Canonical Pathways, and Reactome Gene Sets. The interactive visualization was generated by Metascape (https:// metascape.org/gp/index.html). As a result, 11 and 8 co-expressed gene modules were identified in skin specimen of dcSSc and consensus group of dcSSc-HC (Fig. 1a). Of note, magenta module in dcSSc was identified as specific gene cluster in skin lesion of dcSSc (i.e., labeled in gray, which is unassigned, in the consensus network). Correspondingly, principal component analysis using gene list in magenta module of dcSSc demonstrated expression profiling of the genes in dcSSc was distinct from that of HC (Fig. 1b). Functi
Data Loading...
