Circulating tRNA fragments as a novel biomarker class to distinguish acute stroke subtypes

T. Truc My Nguyen; M. Leontien van der Bent; Marieke J.H. Wermer; Ido R. van den Wijngaard; Erik W. van Zwet; Bas de Groot; Paul H.A. Quax; Nyika D. Kruyt; Anne Yaël Nossent

doi:10.3390/ijms22010135

Circulating tRNA fragments as a novel biomarker class to distinguish acute stroke subtypes

T. Truc My Nguyen, M. Leontien van der Bent, Marieke J.H. Wermer, Ido R. van den Wijngaard, Erik W. van Zwet, Bas de Groot, Paul H.A. Quax, Nyika D. Kruyt^*, Anne Yaël Nossent

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

18 Citationer (Scopus)

Abstract

Early blood biomarkers to diagnose acute stroke could drastically reduce treatment de-lays. We investigated whether circulating small non-coding RNAs can serve as biomarkers to distinguish between acute ischemic stroke (IS), intracerebral hemorrhage (ICH) and stroke mimics (SM). In an ongoing observational cohort study, we performed small RNA-sequencing in plasma obtained from a discovery cohort of 26 patients (9 IS, 8 ICH and 9 SM) presented to the emergency department within 6 h of symptom onset. We validated our results in an independent dataset of 20 IS patients and 20 healthy controls. ICH plasma had the highest abundance of ribosomal and tRNA-derived fragments, while microRNAs were most abundant in plasma of IS patients. Combinations of four to five tRNAs yielded diagnostic accuracies (areas under the receiver operating characteristics curve) up to 0.986 (ICH vs. IS and SM) in the discovery cohort. Validation of the IS and SM models in the independent dataset yielded diagnostic accuracies of 0.870 and 0.885 to distinguish IS from healthy controls. Thus, we identified tRNA-derived fragments as a promising novel class of biomarkers to distinguish between acute IS, ICH and SM, as well as healthy controls.

Originalsprog	Engelsk
Artikelnummer	135
Tidsskrift	International Journal of Molecular Sciences
Vol/bind	22
Udgave nummer	1
Sider (fra-til)	1-10
Antal sider	10
ISSN	1661-6596
DOI	https://doi.org/10.3390/ijms22010135
Status	Udgivet - 1 jan. 2021
Udgivet eksternt	Ja

Bibliografisk note

Funding Information:
Funding: This work was supported by the Dutch Heart Foundation as part of the CINTICS project (M.L.v.d.B.) [grant number 2018B031]; the Dutch Brain Foundation (N.D.K. and T.T.M.N.) [grant number HA20 15.01.02]; the Dutch Innovation Fund (N.D.K. and T.T.M.N.) [grant number 3.240]; Health~Holland (N.D.K. and T.T.M.N.) [grant number LSHM16041]; and the Austrian Science Fund (FWF) with a Lise Meitner Fellowship (A.Y.N.) [grant number M-2578-B30]. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

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Citationsformater

Truc My Nguyen, T., van der Bent, M. L., Wermer, M. J. H., van den Wijngaard, I. R., van Zwet, E. W., de Groot, B., Quax, P. H. A., Kruyt, N. D., & Nossent, A. Y. (2021). Circulating tRNA fragments as a novel biomarker class to distinguish acute stroke subtypes. International Journal of Molecular Sciences, 22(1), 1-10. Artikel 135. https://doi.org/10.3390/ijms22010135

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