PB0137 - Diagnostic and predictive value of circulating microRNAs and their regulation of the BDNF signaling pathway in stroke patients

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Ceren Eyileten, DVM, PhD, MSc (she/her/hers)

Senior Researcher
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland

Co-Author(s)

AN

Anna Nowak

PhD Candidate
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland; Doctoral School, Medical University of Warsaw, 02-091, Warsaw, Poland
Warsaw, Mazowieckie, Poland
Zofia Wicik, PhD

Senior Researcher
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland
SD

Salvatore De Rosa

Professor
Division of Cardiology, Department of Medical and Surgical Sciences, "Magna Graecia" University, Catanzaro, Italy.
Catanzaro, Calabria, Italy
MC

Michael Chong

Senior Researcher
Department of Pathology and Molecular Medicine, Population Genomics Program, McMaster University, Hamilton, Canada
Toronto, Ontario, Canada
Guillaume Pare, Medical Doctor (he/him/his)

Professor
Department of Pathology and Molecular Medicine, Population Genomics Program, McMaster University, Hamilton, Canada
Hamilton, Ontario, Canada
MP

Marek Potuła

Professor
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland

Background: Stroke is the second-most common cause of death worldwide.

Aims: We aimed to identify/validate circulating miRNAs, modulated in ischemic stroke(IS) patients to distinguish the most specific biomarkers to facilitate diagnosis and prognosis.

Methods: 2 microarray miRNA profilings performed, validated (RT-qPCR) to explore; diagnostic miRNAs (29 acute IS patients vs 30 controls), predictive miRNAs (24 single stroke vs 24 patients with multiple stroke or TIA (NAVIGATE-ESUS,ClinicalTrials, NCT02313909).

Results: Microarray data identified 146 up- and 258 downregulated miRs. Target prediction of those miRNAs showed 67 up- and 125 downregulated miRNAs. Upregulated top miRNAs were associated with BDNF, IL-2 signaling pathway, FSH regulation of apoptosis, Axon guidance, TGF-beta regulation of EC matrix. Downregulated miRNAs were most associated with Neuronal Signaling by NGF. ANKRD52, AGO1 were targeted by all types of DE miRNAs. Most susceptible to regulation by upregulated miRNAs: ANKRD12 and HIF1A and downregulated miRNAs: GNAI2 and GRIN1. Diagnostic: miR-18a5p was higher in IS patients at day1/day7 compared to cntrl(p=0.001,p=0.009,res). MiR-199a5p was higher in acute IS, and stayed upregulated at day7 (p < 0.001,p=0.002,res). MiR-4467 was lower in the IS patients at day1 compared to cntrl (p < 0.001). MiR-3135b was downregulated in IS patients at day1/day7 compared to cntrl (p < 0.001,p < 0.001, res). ROC showed diagnostic value for all studied miRNAs for acute IS (p < 0.01). Predictive:MiR-4786(AUC=0.88;p=0.008),miR-1288(AUC=0.93;p=0.027), miR-548ar3p(AUC=0.85;p=0.009),Let-7e5p(AUC=0.52;p=0.005) and miR-125a5p(AUC=0.52;p=0.008) were upregulated, whereas miR-4676(AUC=0.91;p=0.003)was downregulated, in patients with events. qPCR confirmed the microarray results for all studied miRNAs(p < 0.0001), which showed predictive value for risk of events in ROC(p < 0.0001). Enrichment analysis:IL-2,lipid metabolism,BDNF/MAPK signaling are significantly related to stroke.

Conclusion(s): None of the identified miRNAs were studied in stroke before. All studied miRNAs have diagnostic value for acute IS. Results show predictive significance for the risk of a second stroke. Found miRNAs and pathways have potential diagnostic, prognostic utility in neurovascular diseases. MP,CE,AN:OPUS, National Science Center, Poland;2018/31/B/NZ7/01137.