Moxon, Joseph V., Calcino, Andrew, Kraeuter, Ann-Katrin, Phie, James, Anderson, Georgina, Standley, Glenys, Sealey, Cindy, Jones, Rhondda E., Field, Matt A., and Golledge, Jonathan (2023) A case-control comparison of acute-phase peripheral blood gene expression in participants diagnosed with minor ischaemic stroke or stroke mimics. Human Genomics, 17. 106.

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Abstract

Background Past studies suggest that there are changes in peripheral blood cell gene expression in response to ischaemic stroke; however, the specific changes which occur during the acute phase are poorly characterised. The current study aimed to identify peripheral blood cell genes specifically associated with the early response to ischaemic stroke using whole blood samples collected from participants diagnosed with ischaemic stroke (n = 29) or stroke mimics (n = 27) following emergency presentation to hospital. Long non-coding RNA (lncRNA), mRNA and micro-RNA (miRNA) abundance was measured by RNA-seq, and the consensusDE package was used to identify genes which were differentially expressed between groups. A sensitivity analysis excluding two participants with metastatic disease was also conducted.

Results The mean time from symptom onset to blood collection was 2.6 h. Most strokes were mild (median NIH stroke scale score 2.0). Ten mRNAs (all down-regulated in samples provided by patients experiencing ischaemic stroke) and 30 miRNAs (14 over-expressed and 16 under-expressed in participants with ischaemic stroke) were significantly different between groups in the whole cohort and sensitivity analyses. No significant over-representation of gene ontology categories by the differentially expressed genes was observed. Random forest analysis suggested a panel of differentially expressed genes (ADGRG7 and miRNAs 96, 532, 6766, 6798 and 6804) as potential ischaemic stroke biomarkers, although modelling analyses demonstrated that these genes had poor diagnostic performance.

Conclusions This study provides evidence suggesting that the early response to minor ischaemic stroke is predominantly reflected by changes in the expression of miRNAs in peripheral blood cells. Further work in independent cohorts particularly in patients with more severe stroke is needed to validate these findings and investigate their clinical relevance.

Item ID:	81214
Item Type:	Article (Research - C1)
ISSN:	1479-7364
Copyright Information:	© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Date Deposited:	27 Nov 2023 23:58
FoR Codes:	31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310204 Genomics and transcriptomics @ 50% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases) @ 50%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100%
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