RNA sequencing-derived gene co-expression and drug-gene interaction analysis reveal STAT1 as a potential therapeutic

Michail Baltsiotis1,2, Kleio-Maria Verrou2, Petros P Sfikakis1,2

  • 1First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Abstract

Insights

STAT1 is a key regulator in thrombotic antiphospholipid syndrome (PAPS), integrating immune and regulatory pathways. This finding highlights STAT1 as a promising therapeutic target for PAPS, potentially improving treatment outcomes.

Area of Science:

  • Immunology
  • Genomics
  • Pharmacology

Background:

  • Thrombotic primary antiphospholipid syndrome (PAPS) pathogenesis is not fully understood, and treatment often fails to prevent recurrent thrombosis.
  • Identifying specific molecular pathways and drug targets is crucial for developing novel therapies for PAPS.

Purpose of the Study:

  • To investigate gene co-expression networks in thrombotic PAPS.
  • To identify potential druggable targets and molecular regulators within these networks.

Main Methods:

  • Whole-blood RNA sequencing data from 62 PAPS patients and 29 healthy controls were analyzed.
  • Weighted Gene Co-expression Network Analysis (WGCNA) identified PAPS-associated gene modules.
  • Drug-gene interaction analysis prioritized potential therapeutic targets.

Main Results:

  • Two gene modules (yellow and brown) significantly correlated with PAPS, enriched in immune and transcriptional pathways.
  • STAT1 (Transducer and Activator of Transcription 1) emerged as a central hub gene, co-regulating both modules.
  • STAT1 showed strong pharmacological support and was among the top-ranked druggable targets.

Conclusions:

  • STAT1 is a central regulator in PAPS, linking immune and regulatory gene expression.
  • STAT1 represents a promising therapeutic target for thrombotic PAPS.

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