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Circulating miRNA Signature as a Potential Biomarker for the Prediction of Analgesic Efficacy of Hydromorphone

No practical biomarkers currently exist for the prediction of the analgesic efficacy of opioids. Previously, we reported circulating miRNA signatures differentially regulated by µ-opioid receptor (MOR) agonists in healthy subjects. We hypothesized that these miRNAs could be potential pharmacodynamic...

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Autores principales: Kiyosawa, Naoki, Watanabe, Kenji, Toyama, Kaoru, Ishizuka, Hitoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480077/
https://www.ncbi.nlm.nih.gov/pubmed/30987164
http://dx.doi.org/10.3390/ijms20071665
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author Kiyosawa, Naoki
Watanabe, Kenji
Toyama, Kaoru
Ishizuka, Hitoshi
author_facet Kiyosawa, Naoki
Watanabe, Kenji
Toyama, Kaoru
Ishizuka, Hitoshi
author_sort Kiyosawa, Naoki
collection PubMed
description No practical biomarkers currently exist for the prediction of the analgesic efficacy of opioids. Previously, we reported circulating miRNA signatures differentially regulated by µ-opioid receptor (MOR) agonists in healthy subjects. We hypothesized that these miRNAs could be potential pharmacodynamic biomarkers to estimate MOR stimulation, and predict the efficacy of opioids; i.e., patients with low MOR stimulation may be more vulnerable to strengthening of the MOR signal upon hydromorphone treatment. To test this hypothesis, plasma samples were obtained from 25 patients with cancer pain prior to the initiation of hydromorphone treatment and the circulating miRNA levels were evaluated, focusing on four miRNAs (i.e., hsa-miR-423-3p, hsa-let-7a-5p, hsa-miR-26a-5p, and hsa-let-7f-5p) and four miRNAs (i.e., hsa-miR-144-3p, hsa-miR-451a, hsa-miR-215, and hsa-miR-363-3p) that were most clearly up and downregulated by hydromorphone and oxycodone. The patients were classified into two classes with putative high and low MOR signal, estimated based on the plasma miRNA signature. A significant correlation was observed between the analgesic efficacy and the putative MOR signal level, and patients with low MOR signal achieved better pain control (i.e., ΔVAS < 0) through hydromorphone. These results suggested that plasma miRNA signatures could serve as clinical biomarkers for the prediction of the analgesic efficacy of hydromorphone.
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spelling pubmed-64800772019-04-29 Circulating miRNA Signature as a Potential Biomarker for the Prediction of Analgesic Efficacy of Hydromorphone Kiyosawa, Naoki Watanabe, Kenji Toyama, Kaoru Ishizuka, Hitoshi Int J Mol Sci Article No practical biomarkers currently exist for the prediction of the analgesic efficacy of opioids. Previously, we reported circulating miRNA signatures differentially regulated by µ-opioid receptor (MOR) agonists in healthy subjects. We hypothesized that these miRNAs could be potential pharmacodynamic biomarkers to estimate MOR stimulation, and predict the efficacy of opioids; i.e., patients with low MOR stimulation may be more vulnerable to strengthening of the MOR signal upon hydromorphone treatment. To test this hypothesis, plasma samples were obtained from 25 patients with cancer pain prior to the initiation of hydromorphone treatment and the circulating miRNA levels were evaluated, focusing on four miRNAs (i.e., hsa-miR-423-3p, hsa-let-7a-5p, hsa-miR-26a-5p, and hsa-let-7f-5p) and four miRNAs (i.e., hsa-miR-144-3p, hsa-miR-451a, hsa-miR-215, and hsa-miR-363-3p) that were most clearly up and downregulated by hydromorphone and oxycodone. The patients were classified into two classes with putative high and low MOR signal, estimated based on the plasma miRNA signature. A significant correlation was observed between the analgesic efficacy and the putative MOR signal level, and patients with low MOR signal achieved better pain control (i.e., ΔVAS < 0) through hydromorphone. These results suggested that plasma miRNA signatures could serve as clinical biomarkers for the prediction of the analgesic efficacy of hydromorphone. MDPI 2019-04-03 /pmc/articles/PMC6480077/ /pubmed/30987164 http://dx.doi.org/10.3390/ijms20071665 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kiyosawa, Naoki
Watanabe, Kenji
Toyama, Kaoru
Ishizuka, Hitoshi
Circulating miRNA Signature as a Potential Biomarker for the Prediction of Analgesic Efficacy of Hydromorphone
title Circulating miRNA Signature as a Potential Biomarker for the Prediction of Analgesic Efficacy of Hydromorphone
title_full Circulating miRNA Signature as a Potential Biomarker for the Prediction of Analgesic Efficacy of Hydromorphone
title_fullStr Circulating miRNA Signature as a Potential Biomarker for the Prediction of Analgesic Efficacy of Hydromorphone
title_full_unstemmed Circulating miRNA Signature as a Potential Biomarker for the Prediction of Analgesic Efficacy of Hydromorphone
title_short Circulating miRNA Signature as a Potential Biomarker for the Prediction of Analgesic Efficacy of Hydromorphone
title_sort circulating mirna signature as a potential biomarker for the prediction of analgesic efficacy of hydromorphone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480077/
https://www.ncbi.nlm.nih.gov/pubmed/30987164
http://dx.doi.org/10.3390/ijms20071665
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