4.3 Article

Circulating microRNA-30a-5p, microRNA-101-3p, microRNA-140-3p and microRNA-141-3p as potential biomarkers for dexmedetomidine response in pediatric patients

Journal

EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
Volume 77, Issue 12, Pages 1853-1859

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s00228-021-03178-x

Keywords

alpha(2)-Adrenoceptor; Dexmedetomidine; Biomarker; microRNA

Funding

  1. National Key Research and Development Program [:2020ZX09201021]
  2. Guangdong Provincial Key Laboratory of Construction Foundation [:2020B1212060034]
  3. National Natural Science Foundation of China [:81901385]
  4. Guangdong Medical Science and Technology Research Project [A2019367]
  5. Guangzhou Women and Children's Medical Center/Guangzhou Institute of Pediatrics [Pre-PI-2019-011]

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Our study showed that circulating miR-101-3p, miR-140-3p, and miR-30a-5p could serve as blood-based markers for predicting dexmedetomidine efficacy and safety in pediatric patients, with potential discriminatory ability between responders and non-responders, as well as patients with adverse effects.
Purpose The aim of this study was to investigate the expression levels of plasma miR-30a-5p, miR-101-3p, miR-140-3p and miR-141-3p and their relationship to dexmedetomidine efficacy and adverse effects in pediatric patients. Methods The expression levels of miR-30a-5p, miR-101-3p, miR-140-3p and miR-141-3p were measured by qRT-PCR in plasma of 133 pediatric patients receiving dexmedetomidine for preoperative sedation. We analyzed the relationship between miRNA abundance and dexmedetomidine response, including sedative effect and adverse effects, and assessed the predictive power of miRNAs for drug response. Results Among 133 pediatric patients, 111 patients were dexmedetomidine responders (UMSS >= 2) and 22 patients were non-responders (UMSS < 2). We observed higher expression levels of miR-101-3p and miR-140-3p in dexmedetomidine responders compared with non-responders (P < 0.05, P < 0.0001). In contrast, there was no significant difference in the expression levels of miR-30a-5p and miR-141-3p between responders and non-responders (P > 0.05). The plasma levels of miR-101-3p and miR-30a-5p were markedly downregulated in patients who experienced hypotension and bradycardia, respectively (P < 0.05). MiR-101-3p and miR-140-3p demonstrated a potential discriminatory ability between dexmedetomidine responders and non-responders, with AUC of 0.64 (P < 0.05) and 0.77 (P < 0.0001), respectively. The AUC of miR-101-3p in distinguishing patients without hypotension was 0.63 (P < 0.05). The AUC of miR-30a-5p in distinguishing patients without bradycardia was 0.74 (P < 0.05). Conclusion Our study demonstrated that circulating miR-101-3p, miR-140-3p and miR-30a-5p might be used as a blood-based marker for dexmedetomidine efficacy and safety in pediatric patients.

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