BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
RNA Sequencing-derived Gene Co-expression and Drug-Gene Interaction Analysis reveal STAT1 as a potential Therapeutic Target in Thrombotic Antiphospholipid Syndrome
School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece
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Abstract
Objective: Identifying disease-specific molecular pathways and regulators can help in the discovery of novel therapeutic targets. Herein, we examine gene co-expression networks and potential druggable targets in thrombotic PAPS. Methods: We analyzed a whole-blood RNA-sequencing dataset from 62 well-characterized patients with thrombotic PAPS (40% with recurrent thrombosis), and 29 age/sex-matched healthy controls(HCs). Weighted Gene Co-expression Network Analysis (WGCNA) was performed to identify gene modules associated with PAPS, followed by enrichment analysis. DruggabilityDrug-gene interaction analysis of hub regulators within the identified networks was applied. Genes were classified based on target drug annotation into three druggability and priority categories (low/medium/ high). Results: WGCNA of whole-blood transcriptome of thrombotic PAPS and HCs, which included 8,190 expressed genes, identified five co-expression modules, two of which correlated with PAPS: the yellow, consisted of 42 genes enriched in immune-related functions, and the brown comprised 144 genes with a regulatory signature enriched in transcription activation pathways. A merged module demonstrated enhanced correlation with PAPS compared with HCs (r=0.221, p=0.035). Both yellow and brown, and merged module, were co-regulated by Transducer and Activator of Transcription 1 (STAT1), which emerged as a central hub gene. STAT1 was also present in 5 of 6 immune-related pathways. In druggabilitydrug-gene interaction analysis, STAT1 3 was among the four highly-ranked genes, and displayed many interactions and strong pharmacological support. Conclusion: STAT1 is identified as a central regulator of gene expression networks in PAPS, integrating both immune-related and regulatory processes. Druggability analysis Assessment of pharmacological target availability revealed STAT1 as a promising treatment target.
Summary
Keywords
Antiphospholipid Syndrome, Gene co-expression network analysis, interferon, RNA sequencing, Transducer and Activator of Transcription 1 (STAT1)
Received
07 November 2025
Accepted
17 February 2026
Copyright
© 2026 Baltsiotis, Verrou, Sfikakis and Tektonidou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Maria G Tektonidou
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