Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis

Yue-Mei Yan; Meng-Zhu Jin; Sheng-Hua Li; Yun Wu; Qiang Wang; Fei-Fei Hu; Chen Shen; Wen-Hao Yin

doi:10.3389/fgene.2023.1202561

Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis

Front Genet. 2023 Jul 12:14:1202561. doi: 10.3389/fgene.2023.1202561. eCollection 2023.

Authors

Yue-Mei Yan¹, Meng-Zhu Jin¹, Sheng-Hua Li¹, Yun Wu¹, Qiang Wang², Fei-Fei Hu², Chen Shen³, Wen-Hao Yin¹

Affiliations

¹ Department of Dermatology, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, China.
² Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
³ Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University, Shanghai, China.

Abstract

Background: Systemic sclerosis (scleroderma; SSc), a rare and heterogeneous connective tissue disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. The purpose of the present study was to identify hub genes, diagnostic markers and explore potential small-molecule drugs of SSc. Methods: The cohorts of data used in this study were downloaded from the Gene Expression Complex (GEO) database. Integrated bioinformatic tools were utilized for exploration, including Weighted Gene Co-Expression Network Analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, gene set enrichment analysis (GSEA), Connectivity Map (CMap) analysis, molecular docking, and pharmacokinetic/toxicity properties exploration. Results: Seven hub genes (THY1, SULF1, PRSS23, COL5A2, NNMT, SLCO2B1, and TIMP1) were obtained in the merged gene expression profiles of GSE45485 and GSE76885. GSEA results have shown that they are associated with autoimmune diseases, microorganism infections, inflammatory related pathways, immune responses, and fibrosis process. Among them, THY1 and SULF1 were identified as diagnostic markers and validated in skin samples from GSE32413, GSE95065, GSE58095 and GSE125362. Finally, ten small-molecule drugs with potential therapeutic effects were identified, mainly including phosphodiesterase (PDE) inhibitors (BRL-50481, dipyridamole), TGF-β receptor inhibitor (SB-525334), and so on. Conclusion: This study provides new sights into a deeper understanding the molecular mechanisms in the pathogenesis of SSc. More importantly, the results may offer promising clues for further experimental studies and novel treatment strategies.

Keywords: connectivity map; molecular docking; phosphodiesterase inhibitors; systemic sclerosis; weighted gene co-expression network analysis.

Grants and funding

This research was funded by the grants from Zhejiang medical and health science and technology program (grant number: No.2022KY1243) and the Jiaxing Key Discipline of Chinese Medicine Dermatology and Venereology of Integrative Medicine (grant number: No.2019XK-C06).