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

• Published in: PLOS Neglected Tropical Diseases
• Main Authors: Umaporn Limothai, Nattawat Jantarangsi, Natthasit Suphavejkornkij, Sasipha Tachaboon, Janejira Dinhuzen, Watchadaporn Chaisuriyong, Supachoke Trongkamolchai, Mananya Wanpaisitkul, Chatchai Chulapornsiri, Anongrat Tiawilai, Thawat Tiawilai, Terapong Tantawichien, Usa Thisyakorn, Nattachai Srisawat
• Format: Article in Journal/Newspaper
• Language: English
• Published: Public Library of Science (PLoS) 2022
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Public aspects of medicine; RA1-1270; Arctic
• Online Access: https://doi.org/10.1371/journal.pntd.0010836; https://doaj.org/article/f18d45460e034f59868ca45b67632507

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.