RNA sequencing-derived gene co-expression and drug-gene interaction analysis reveal STAT1 as a potential therapeutic target in thrombotic antiphospholipid syndrome.
Baltsiotis M, Verrou K, Sfikakis P, Tektonidou M • Frontiers in immunology • 2026
STAT1 is identified as a central regulator of gene expression networks in thrombotic primary antiphospholipid syndrome, integrating both immune-related and regulatory processes, and assessment of pharmacological target availability revealed STAT1 as a promising treatment target.
Key Findings
Results
WGCNA of whole-blood transcriptome identified five co-expression modules in thrombotic PAPS, two of which correlated with PAPS.
Analysis included 8,190 expressed genes from 62 patients with thrombotic PAPS and 29 age/sex-matched healthy controls.
The yellow module consisted of 42 genes enriched in immune-related functions.
The brown module comprised 144 genes with a regulatory signature enriched in transcription activation pathways.
40% of the thrombotic PAPS patients had recurrent thrombosis.
Results
A merged module combining the yellow and brown modules demonstrated enhanced correlation with PAPS compared with healthy controls.
The merged module showed a correlation of r=0.221, p=0.035 with PAPS status.
Both yellow and brown modules were individually correlated with PAPS before merging.
The merged module was co-regulated by STAT1 as a central hub gene.
Results
STAT1 emerged as the central hub gene co-regulating both PAPS-associated co-expression modules.
STAT1 (Transducer and Activator of Transcription 1) was identified as a hub regulator in both the yellow and brown modules, as well as the merged module.
STAT1 was present in 5 of 6 immune-related pathways identified in enrichment analysis.
STAT1 integrated both immune-related and regulatory transcriptional processes.
Results
Drug-gene interaction analysis identified STAT1 as one of four highly-ranked genes with strong pharmacological support.
Genes were classified based on target drug annotation into priority categories: low, medium, and high.
STAT1 displayed many drug-gene interactions and strong pharmacological support.
STAT1 was among the four genes assigned the highest priority category in drug-gene interaction analysis.
Methods
The study population comprised 62 well-characterized patients with thrombotic primary antiphospholipid syndrome and 29 healthy controls analyzed by whole-blood RNA sequencing.
Patients and controls were age/sex-matched.
40% of the PAPS patients had recurrent thrombosis despite presumably adequate anticoagulation.
Whole-blood RNA sequencing yielded 8,190 expressed genes that were included in the WGCNA analysis.
Baltsiotis M, Verrou K, Sfikakis P, Tektonidou M. (2026). RNA sequencing-derived gene co-expression and drug-gene interaction analysis reveal STAT1 as a potential therapeutic target in thrombotic antiphospholipid syndrome.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1741872