A case-control comparison of acute-phase peripheral blood gene expression in participants diagnosed with minor ischaemic stroke or stroke mimics.
Ischaemic stroke
Peripheral blood gene expression
RNA-seq
Stroke mimics
miRNA
Journal
Human genomics
ISSN: 1479-7364
Titre abrégé: Hum Genomics
Pays: England
ID NLM: 101202210
Informations de publication
Date de publication:
25 Nov 2023
25 Nov 2023
Historique:
received:
29
08
2023
accepted:
11
11
2023
medline:
27
11
2023
pubmed:
26
11
2023
entrez:
25
11
2023
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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.
Identifiants
pubmed: 38007520
doi: 10.1186/s40246-023-00551-y
pii: 10.1186/s40246-023-00551-y
pmc: PMC10676587
doi:
Substances chimiques
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106Informations de copyright
© 2023. The Author(s).
Références
J Stat Softw. 2010;33(1):1-22
pubmed: 20808728
JPGN Rep. 2023 May 09;4(2):e309
pubmed: 37200712
Neuropsychiatr Dis Treat. 2020 Jan 13;16:153-160
pubmed: 32021207
Int J Mol Sci. 2022 Mar 21;23(6):
pubmed: 35328807
Lancet. 2020 Jul 11;396(10244):129-142
pubmed: 32653056
PLoS One. 2013 Jun 18;8(6):e66393
pubmed: 23823624
Nucleic Acids Res. 2020 Jan 8;48(D1):D127-D131
pubmed: 31504780
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Front Neurol. 2019 Feb 01;10:36
pubmed: 30774621
Stroke. 1993 Jan;24(1):35-41
pubmed: 7678184
Front Cardiovasc Med. 2022 Oct 06;9:1024790
pubmed: 36277770
J Cereb Blood Flow Metab. 2008 Jul;28(7):1320-8
pubmed: 18382470
J Cell Mol Med. 2020 Sep;24(17):9590-9604
pubmed: 32666704
Mol Ther. 2022 Apr 6;30(4):1675-1691
pubmed: 35077859
Int J Mol Sci. 2022 Dec 21;24(1):
pubmed: 36613546
Brain Behav. 2017 Dec 30;8(1):e00835
pubmed: 29568675
Cell Mol Gastroenterol Hepatol. 2023;15(4):1022-1026
pubmed: 36592862
Medicine (Baltimore). 2021 Jan 29;100(4):e24184
pubmed: 33530209
Pharmacogenomics. 2021 Oct;22(15):973-982
pubmed: 34521259
Atherosclerosis. 2017 Aug;263:301-308
pubmed: 28728066
Sci Rep. 2020 Jun 23;10(1):10138
pubmed: 32576868
Int J Mol Sci. 2022 Apr 23;23(9):
pubmed: 35563054
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
PeerJ. 2019 Dec 13;7:e8206
pubmed: 31844586
Front Mol Biosci. 2021 May 21;8:682769
pubmed: 34095232
BMC Med. 2023 Feb 20;21(1):65
pubmed: 36803375
BMC Cardiovasc Disord. 2015 Jun 16;15:51
pubmed: 26077801
Mol Med Rep. 2021 Dec;24(6):
pubmed: 34726256
PLoS One. 2017 Feb 15;12(2):e0172131
pubmed: 28199366
J Stroke Cerebrovasc Dis. 2018 Mar;27(3):522-530
pubmed: 29128328
Stroke. 2019 Nov;50(11):3259-3264
pubmed: 31510897
DNA Cell Biol. 2021 Mar;40(3):457-468
pubmed: 33493415
Pediatr Surg Int. 2022 Dec;38(12):2023-2034
pubmed: 36271952
Int J Mol Sci. 2023 May 23;24(11):
pubmed: 37298078
Mol Med Rep. 2019 Jun;19(6):5203-5210
pubmed: 31059039
J Cereb Blood Flow Metab. 2021 Jun;41(6):1398-1416
pubmed: 32960689
Transl Stroke Res. 2015 Aug;6(4):284-9
pubmed: 25994285
Heart Vessels. 2023 Mar;38(3):318-331
pubmed: 36214846
Circ Cardiovasc Genet. 2014 Feb;7(1):71-9
pubmed: 24448739
Ann Med. 2015;47(6):468-73
pubmed: 26333279
Circ Res. 2017 Sep 29;121(8):970-980
pubmed: 28724745
Heart Fail Rev. 2021 Jul;26(4):997-1021
pubmed: 33443726
J Dermatolog Treat. 2021 Dec;32(8):973-982
pubmed: 32079424
BMC Cardiovasc Disord. 2022 Nov 4;22(1):462
pubmed: 36333663
Biol Open. 2019 Jan 14;8(1):
pubmed: 30598481
Front Neurosci. 2022 Jun 10;16:901360
pubmed: 35757539
Bioengineered. 2022 Apr;13(4):8667-8675
pubmed: 35322734
Metab Brain Dis. 2022 Mar;37(3):665-676
pubmed: 35067794
Ann Clin Transl Neurol. 2016 Jan 15;3(2):70-81
pubmed: 26900583
Int Immunopharmacol. 2022 Jul;108:108743
pubmed: 35413679
J Stroke. 2023 May;25(2):251-265
pubmed: 37106564
BMC Neurol. 2021 Sep 25;21(1):370
pubmed: 34563140
Biosci Rep. 2016 Jun 30;36(3):
pubmed: 27190129
Exp Anim. 2021 Feb 6;70(1):126-136
pubmed: 33116025
J Headache Pain. 2023 Feb 17;24(1):11
pubmed: 36797674
Front Cell Dev Biol. 2021 Jun 21;9:685741
pubmed: 34239876
Lancet Neurol. 2021 Oct;20(10):795-820
pubmed: 34487721
PLoS Med. 2007 Oct 16;4(10):e297
pubmed: 17941715
J Cell Mol Med. 2022 Oct;26(20):5135-5149
pubmed: 36117396