Association of microRNAs as biomarkers for severe liver dysfunction in severe dengue infection

Abstract

Background: The identification of early biomarkers to predict liver dysfunction in patients with severe dengue is essential. Currently, there is no available data on circulating microRNAs to predict this important complication.

Objectives: This study aimed to explore the role of circulating microRNAs in predicting severe liver dysfunction in dengue infection by identifying and validating predictive microRNAs via NanoString and quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

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 and non-severe liver dysfunction groups. To perform transcriptomic analysis of the circulating microRNAs, we used the NanoString nCounter 1 Human v3 microRNA Expression Assays. Subsequently, we validated the levels of the selected microRNAs using qRTPCR.

Results: In the discovery phase, 5 non-severe cases and 4 severe cases were tested, and elevated liver enzymes were found in the severe cases. In the validation phase, 11 severe cases demonstrated substantially longer durations of fever before admission; higher white blood cell counts, total bilirubin, direct bilirubin, and liver enzyme levels; and lower platelet counts and abdominal pain, compared with those of the 92 non-severe cases. Analysis revealed that only 2 of 798 microRNAs, microRNA-424-5p and microRNA-30d-5p, were upregulated in the non-severe group compared to the severe group, and only microRNA-424-5p was significantly higher. microRNA-424-5p had an area under the receiver operating characteristic curve of 0.67 (95% confidence interval: 0.52–0.86, P = 0.04) and exhibited sensitivity, specificity, positive predictive value, and negative predictive value of 63.6%, 76.1%, 16.3%, and 83.7%, respectively. Functional enrichment and gene-targeting analyses indicated that microRNA-424-5p may influence important signaling pathways, including mitogen-activated protein kinase, PI3K-Akt, and mTOR, which are involved in cellular development and metabolic regulation.

Conclusion: Notably, microRNA-424-5p exhibited modest diagnostic performance in distinguishing severe from non-severe liver dysfunction. Our research highlighted the potential of circulating microRNAs, particularly microRNA-424-5p, as biomarkers for predicting severe liver dysfunction in patients with dengue.