Identification of GATA2-AS1- hsa-miR-125b-5p-PLAU ceRNA regulatory network as novel biomarkers for prethrombotic state in patients with coronary artery disease

Current diagnostic tools lack specificity for identifying the prethrombotic state (PTS), a critical precursor to coronary thrombosis in coronary artery disease (CAD). This study aimed to discover and validate specific multi-omics biomarkers for PTS detection to enable early intervention. Integrated transcriptomic and proteomic analyses were performed on peripheral blood mononuclear cells (PBMCs) and plasma from a discovery cohort (n = 28), including healthy controls, stable CAD patients without PTS (NPTS), with PTS, and acute myocardial infarction (AMI) patients. Multi-omics profiling revealed 43 proteins, 334 mRNAs, 27 miRNAs, 253 lncRNAs, and 8 circRNAs as candidate biomarkers, from which a complement and coagulation cascade–related ceRNA subnetwork was extracted. Within this network, nine hub RNAs and two proteins were prioritized, and validation in an independent cohort (n = 40) identified the GATA2-AS1/miR-125b-5p/PLAU axis together with FVIII protein as significantly dysregulated in PTS. These biomarkers showed strong diagnostic performance for distinguishing PTS from NPTS: FVIII (AUC 0.88, 95% CI 0.73-1.00), PLAU (AUC 0.95, 95% CI 0.86-1.00), hsa-miR-125b-5p (AUC 0.78, 95% CI 0.57–0.99), and GATA2-AS1 (AUC 0.89, 95% CI 0.74-1.00). The GATA2-AS1/miR-125b-5p/PLAU-FVIII panel enables accurate PTS detection for early intervention.