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Transfer RNAs are linked to ischemic stroke and major bleeding in patients with end-stage kidney disease

医学 小RNA 终末期肾病 冲程(发动机) 人口 病例对照研究 疾病 生物信息学 肿瘤科 内科学 生物 遗传学 基因 机械工程 环境卫生 工程类
作者
Stephan Nopp,Oliver Königsbrügge,Sabine Schmaldienst,Marcus D. Säemann,Ingrid Pabinger,A. Yaël Nossent,Cihan Ay
出处
期刊:Thrombosis and Haemostasis [Thieme Medical Publishers (Germany)]
标识
DOI:10.1055/a-2413-2792
摘要

Background: Patients with end-stage kidney disease (ESKD) are at very high risk for thromboembolism and bleeding. This study aimed to identify small non-coding RNAs (sncRNAs), specifically microRNAs and transfer-RNA (tRNA)-derived fragments (tRFs), as potential novel biomarkers for predicting thromboembolism and bleeding in this high-risk population. Methods: In this sncRNA discovery research, we leveraged the VIVALDI cohort, consisting of 625 ESKD patients on hemodialysis, to conduct two nested case-control studies, each comprising 18 participants. The primary outcomes were ischemic stroke in the first study and major bleeding in the second. Plasma samples were processed using the miND pipeline for RNA-seq analysis to investigate differential expression of microRNAs and tRNA/tRFs between cases and their respective matched controls, with results stringently adjusted for false discovery rate (FDR). Results: No significant differential expression of microRNAs for either ischemic stroke or major bleeding outcomes was observed in the two nested case-control studies. However, we identified four tRNAs significantly differentially expressed in ischemic stroke cases and seven in major bleeding cases, compared to controls (FDR<0.1). Coverage plots indicated that specific tRNA fragments (tRFs), rather than full-length tRNAs, were detected, however. Alternative mapping approaches revealed challenges and technical limitations that precluded in-depth differential expression analyses on these specific tRFs. Yet, they also underscored the potential of tRNAs and tRFs as markers for thromboembolism and bleeding. Conclusion: While microRNAs did not show significant differential expression, our study identifies specific tRNAs/tRFs as potential novel biomarkers for ischemic stroke and major bleeding in ESKD patients.
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