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Plasma-derived exosomal miRNA profiling in dengue patients with and without warning signs

ABSTRACT: Dengue virus infection is recognized as one of the most important mosquitos borne human diseases of the 21st century. It can manifest clinically as a moderate febrile illness, or a severe life-threatening disease called dengue haemorrhagic fever. Notably, there are currently no predictive diagnostic values for individuals prone to bleeding manifestations associated with this infection. This study explores the potential solution by focusing on exosomes, lipid vesicles enriched in specific microRNA. These exosomal microRNAs have the potential to form a disease-specific diagnostic signature, paving the way for an analysis of exosomal plasma microRNA expression to predict bleeding tendency in dengue infection. In total, 6 blood plasma exosome samples, dengue without warning sign (n = 3) and dengue with warning sign (n = 3) were used to isolate total RNA. Small RNA analysis and microarray-based expression profiling was used to detect the miRNA profile of plasma exosomes to identify predictive biomarker for bleeding manifestations in patients with warning sign as compared to patients without warning signs. Microarray profiling revealed that 24 miRNAs were upregulated in the plasma derived exosome miRNA in the dengue patients with warning signs. Functional analysis of target genes of these miRNAs in silico indicated their involvement in bleeding manifestation in dengue infection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE307678 | GEO | 2025/09/12

REPOSITORIES: GEO

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Project description:This pilot study, aimed to profile the host transcriptome as a potential strategy for identifying specific biomarkers for dengue prediction and detection. High-throughput RNA-sequencing (RNA-seq) was employed to generate host transcriptome profiles in 16 dengue patients and 10 healthy controls. Differentially expressed genes (DEGs) were identified in patients with severe dengue and those with dengue with warning signs compared to healthy individuals. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the functions of upregulated and downregulated genes. Compared to healthy controls, 6466 genes were significantly differentially expressed (P < 0.05) in the dengue with warning signs group and 3082 genes in the severe dengue group, with over half being upregulated. The major KEGG pathways implicated included transport and catabolism (14.4%-16.3%), signal transduction (6.6%-7.3%), global and overview maps (6.7%-7.1%), viral diseases (4.6%-4.8%), and the immune system (4.4%-4.6%). Several genes exhibited consistent and significant upregulation across all dengue patients, regardless of severity: Interferon alpha inducible protein 27 (IFI27), Potassium Channel Tetramerisation Domain Containing 14 (KCTD14), Syndecan 1 (SDC1), DCC netrin 1 receptor (DCC), Ubiquitin C-terminal hydrolase L1 (UCHL1), Marginal zone B and B1 cell specific protein (MZB1), Nestin (NES), C-C motif chemokine ligand 2 (CCL2), TNF receptor superfamily member 17 (TNFSF17), and TNF receptor superfamily member 13B (TNFRSF13B). Further analysis revealed potential biomarkers for severe dengue prediction, including TNF superfamily member 15 (TNFSF15), Plasminogen Activator Inhibitor-2 (SERPINB2), motif chemokine ligand 7 (CCL7), aconitate decarboxylase 1 (ACOD1), Metallothionein 1G (MT1G) and Myosin Light Chain Kinase (MYLK2), which were expressed 3.5 times, 2.9 times, 2.3 times, 2.1 times, 1.7 times, and 1.4 times greater, respectively, than dengue patients exhibiting warning signs. The identification of these host biomarkers through RNA-sequencing holds promising implications and potential to augment existing dengue detection algorithms, contributing significantly to improved diagnostic and prognostic capabilities.

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Plasma-derived exosomal miRNA profiling in dengue patients with and without warning signs

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