Serum miRNA-based risk prediction for stroke
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ABSTRACT:
PROVIDER: PRJNA480974 | ENA |
REPOSITORIES: ENA
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Project description:The serum miRNAs were correlated with predicted the incidence of stroke.
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Project description:Atrial fibrillation (AF) is a major risk factor for cardioembolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern particularly when antiplatelet treatment is simultaneously administered. Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke identified a stroke related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was downregulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out (KO) mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts. In WT mice, Hsp70 inducers (TRC051384, or tubastatin A) delayed thrombus formation. Remarkably, Hsp70 inducers did not increase the bleeding risk even when aspirin was concomitantly administered. Hsp70 induction was associated with an increased vascular thrombomodulin expression, higher circulating levels of activated protein C (APC) upon thrombotic stimulus and increased protection against endothelial apoptosis. Thus, Hsp70 induction is a novel approach to delay thrombus formation with minimal bleeding risk, being especially promising in situations where there is a major bleeding hazard. Microarray analysis in peripheral blood cells includes eight patients with AF and stroke and eight AF subjects without stroke
2016-04-01 | E-GEOD-66724 | biostudies-arrayexpress
Project description:Hemorrhagic transformation (HT), which occurs with or without reperfusion treatments (thrombolysis and/or thrombectomy), deteriorates the outcomes of ischemic stroke patients. It is essential to find clinically reliable biomarkers that can predict HT. In this study, we screened for potential serum biomarkers from an existing blood bank and database with 243 suspected acute ischemic stroke (AIS) patients. A total of 37 patients were enrolled, who were diagnosed as AIS but did not receive reperfusion treatment. They were divided into two groups based on whether they accompanied with HT or not (5 HT and 32 non-HT). Serum samples were labeled by isobaric tags for relative and absolute quantitation (iTRAQ) and analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and compared under NCBInr database. A total of 647 proteins in sera samples were captured and the levels of 17 proteins (12 up-regulated and 5 down-regulated) were significantly different. These differentially expressed proteins were further categorized with Gene Ontology functional classification annotation and Kyoto Encyclopedia of Genes and Genomes metabolic pathway analysis into biological processes. Further protein-protein interaction analysis using String database discovered that, among the differential expressed proteins, 10 pairs of proteins were found to have crosstalk connections, which may have direct (physical) and indirect (functional) interactions for the development of HT. Our findings suggest that these differentially expressed proteins could serve as potential biomarkers for predicting HT after ischemic stroke.
2021-10-12 | PXD026950 | Pride
Project description:Circulating microRNAs (c-miRNAs) have emerged as measurable biomarkers (liquid biopsies) for cancer detection. The goal of our study was to identify novel biomarkers to predict long-term breast cancer risk in cancer-free women. We evaluated the ability of c-miRNAs to identify women most likely to develop breast cancer by profiling miRNA from serum obtained long before diagnosis. 24 breast cancer cases and controls (matched for risk and age) were identified from women enrolled in the High-Risk Breast Program at the UVM Cancer Center. We used Affymetrix miRNA v4 microarrays to interrogate miRNAs (miRBase v20) in the serum of cancer-free women at high-risk for breast cancer. The 24 cases developed breast cancer at least 6 months (average of 3.2 years) and the 24 controls remain cancer-free.
2018-01-22 | GSE98181 | GEO
Project description:Long non-coding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only, to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC), using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence “gallstones → dysplasia → GBC”. In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA-expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes, and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2= 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR=1.25 per log2 expression unit, 95%CI 1.04-1.52, p value = 0.02).
2022-01-17 | E-MTAB-11367 | biostudies-arrayexpress
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived retinal transcriptome profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to evaluate protocols for optimal high-throughput data analysis Methods: The serum microvesicles of five acute ischemic stroke (AIS) and healthy controls was purified using Ribo™ Exosome Isolation Reagent (C10110-2, RIBOBIO, Guangzhou, China) and analyzed by flow cytometry and nanoparticle tracking analysis (NTA).The miRNA expression profiles of serum microvesicles of five acute ischemic stroke (AIS) and healthy controls were detected by RNA-seq using llumina HiSeqTM 2500. Results: Using an optimized data analysis workflow, 732 miRNA species were detected in total. The levels of 51 individual miRNA species were significantly different between AIS patients and healthy controls. Conclusions: Our study represents the first detailed analysis of miRNA expression profiles of serum microvesicles in AIS and healthy controls, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of miRNA content in serum microvesicles. We conclude that RNA-seq based non-coding RNA characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.
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Project description:The difference of circulating miRNA expressions by the presence of atherosclerosis in intra- and extra-cranial vessels were evaluated using serum of ischemic stroke patients.
2017-03-16 | GSE96621 | GEO
Project description:Acute stroke, with ischemic stroke comprising 80% of all cerebrovascular incidents, has been recognized as one of the core problems in clinical medicine in need of prevention and treatment. Intravenous rtPA is the mainstay and the highest class evidence based method of acute ischemic stroke treatment, and is currently recommended 0-4.5 hours after stroke onset. In most patients decision on i.v. rtPA administration is striaghtforward, however the biggest concern is the symptomatic intracranial haemorrhage (sICH), which occurs in 3-7% of all treated patients, and is associated with worse 90-day functional outcome and higher disability than in those untreated. Finding a method of the powerful (highly specific and selective) identification of patients at highest risk of sICH, in order to increase the percentage of stroke patients safely treated with rtPA, is one of the most important challenges in stroke research. To address this problem we designed a major and complex project to identify blood, neuroimaging, and clinical biomarkers combined for prospective assessment of the risk of intracranial hemorrhage (ICH) after thrombolytic treatment of acute ischemic stroke. Herein, we reveal our general methodological approach with shortlisting of blood protein candidates selected with Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) that in the future might increase sensitivity and selectivity of the rtPA-associated sICH risk calculations.
2021-11-25 | PXD021713 | Pride