Abstract
Background: Identification early biomarkers for predicting severe liver dysfunction in severe dengue patients is essential. Currently, there is no any data on circulating microRNAs to predict this important complication.
Objectives: This study aimed to explore the role of circulating microRNAs in prediction severe liver dysfunction in dengue infection by identifying and validating predictive microRNAs via Nanostring and RT-qPCR.
Methods: On the initial day of admission, serum samples were gathered from patients with dengue infection. These patients were monitored for 14 days post-admission to ascertain their final diagnosis. Following the WHO 2009 criteria, participants were categorized into severe liver dysfunction and non-severe liver dysfunction group. To conduct a transcriptomic analysis of circulating miRNAs used the NanoString nCounter1Human v3 miRNA Expression Assays. Subsequently, using quantitative reverse transcription-PCR validated the levels of selected microRNAs.
Results: In the discovery phase, 5 non-severe cases and 4 severe cases were tested, and it showed that elevated liver enzymes in severe patients. In the validation phase, 11 severe cases demonstrated significantly longer duration of fever before admission, higher jaundice, white blood cell counts, total bilirubin, direct bilirubin, liver enzymes and lower abdominal pain and platelets, when compared to 92 non-severe cases. Analysis showed only 2 of 798 microRNAs that miR-424-5p and miR-30d-5p were upregulated compared severe group to non-severe group, but only miR-424-5p were significantly higher. miR-424-5p had AUROC of 0.67 (95%CI; 0.516-0.863, p = 0.04), and showed sensitivity, specificity, positive predictive value, negative predictive value of 63.6%, 76.1%, 16.3%, 83.7%. Functional enrichment and gene-targeting analyses suggested that miR-424-5p may influence important signaling pathways, including MAPK, PI3K-Akt, and mTOR pathways, which are involved in cellular development and metabolic regulation.
Conclusions: Notably, miR-424-5p exhibited modest diagnostic performance in distinguishing severe liver dysfunction from non-severe liver dysfunction with an AUC of 0.67. Our research highlighted the potential of circulating microRNAs particularly microRNA-424-5p as potential biomarkers for predicting severe liver dysfunction in severe dengue patients.
DOI
10.56808/2673-060X.5617
Recommended Citation
Pas-arj, Napat; Srisawat, Nattachai; Limothai, Umaporn; Tachaboon, Sasipha; and Dinhuzen, Janejira
(2026)
"Association of miRNAs as biomarkers for severe liver dysfunction in severe dengue infection,"
Chulalongkorn Medical Journal: Vol. 70:
Iss.
3, Article 6.
DOI: https://doi.org/10.56808/2673-060X.5617
Available at:
https://digital.car.chula.ac.th/clmjournal/vol70/iss3/6