Discovery and validation of circulating miRNAs for the clinical prognosis of severe dengue

Abstract

Background Early prognostic markers of severe dengue may improve case management and reduce dengue-related mortalities. This study aimed to identify circulating microRNAs (miRNAs) as biomarkers for predicting severe dengue. Methodology Serum samples from dengue-infected patients were collected on the first day of admission. Patients were followed up for 14 days after admission to determine the final diagnosis. Participants were divided into non-severe and severe dengue, as defined by WHO 2009 criteria. Circulating microtranscriptome analysis was performed using NanoString miRNA Expression Assay. The expression level of candidate miRNAs were then validated by quantitative reverse transcription-PCR method. Principal findings The discovery cohort (N = 19) lead to the identification of 37 differentially expressed miRNAs between the two groups. Six up-regulated candidate miRNAs were selected and further validated in the larger cohort (N = 135). MiR574-5p and miR1246 displayed the highest diagnostic performance in discriminating between severe from non-severe dengue (ROC-AUC = 0.83). Additionally, miR574-5p and miR1246 had high sensitivity and high negative predictive value for detecting severe dengue. Multivariate analysis suggested that serum miR574-5p was an independent predictor of severe dengue (odds ratio 3.30, 95% CI 1.81–6.04; p<0.001). Conclusion Our study indicated that circulating miRNAs, especially miR-574-5p and miR-1246, might be a promising diagnostic and prognostic biomarker for severe dengue upon hospital admission, especially when using these biomarkers on days 1 to 2 before the onset of severe dengue complications.

Common arboviruses and the kidney: a review

“…Small non-coding RNAs, so-called microRNAs (miRNAs), which have a length of 20–22 nucleotides, are important for the post-transcriptional control of gene expression. Patients with severe dengue present a different pattern of miRNA expression, and there are miRNAs that could be used as prognostic markers for dengue severity, the most promising being miR-574-5p and miR-1246 63 .…”

“…Pequenos RNAs não codificadores, os chamados microRNAs (miRNAs), que têm comprimento de 20 a 22 nucleotídeos, são importantes para o controle pós-transcricional da expressão gênica. Os pacientes com dengue grave apresentam um padrão diferente de expressão de miRNA, e há miRNAs que podem ser usados como marcadores prognósticos para a gravidade da dengue, sendo o miR-574-5p e o miR-1246 os mais promissores 63 .…”