Serum miRNA-based signature indicates radiation exposure and dose in humans: A multicenter diagnostic biomarker study.

Autor: Nowicka Z; Department of Biostatistics and Translational Medicine, Medical University of Lodz, Poland., Tomasik B; Department of Biostatistics and Translational Medicine, Medical University of Lodz, Poland; Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Radiotherapy Department, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland., Kozono D; Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Stawiski K; Department of Biostatistics and Translational Medicine, Medical University of Lodz, Poland., Johnson T; Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Haas-Kogan D; Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Ussowicz M; Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, Wroclaw Medical University, Poland., Chowdhury D; Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: Dipanjan_Chowdhury@dfci.harvard.edu., Fendler W; Department of Biostatistics and Translational Medicine, Medical University of Lodz, Poland; Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: Wojciech_fendler@dfci.harvard.edu.
Jazyk: angličtina
Zdroj: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology [Radiother Oncol] 2023 Aug; Vol. 185, pp. 109731. Date of Electronic Publication: 2023 Jun 08.
DOI: 10.1016/j.radonc.2023.109731
Abstrakt: Purpose: Mouse and non-human primate models showed that serum miRNAs may be used to predict the biological impact of radiation doses. We hypothesized that these results can be translated to humans treated with total body irradiation (TBI), and that miRNAs may be used as clinically feasible biodosimeters.
Methods: To test this hypothesis, serial serum samples were obtained from 25 patients (pediatric and adults) who underwent allogeneic stem-cell transplantation and profiled for miRNA expression using next-generation sequencing. miRNAs with diagnostic potential were quantified with qPCR and used to build logistic regression models with lasso penalty to reduce overfitting, identifying samples drawn from patients who underwent total body irradiation to a potentially lethal dose.
Results: Differential expression results were consistent with previous studies in mice and non-human primates. miRNAs with detectable expression in this and two prior animal sets allowed for distinction of the irradiated from non-irradiated samples in mice, macaques and humans, validating the miRNAs as radiation-responsive through evolutionarily conserved transcriptional regulation mechanisms. Finally, we created a model based on the expression of miR-150-5p, miR-30b-5p and miR-320c normalized to two references and adjusted for patient age with an AUC of 0.9 (95%CI:0.83-0.97) for identifying samples drawn after irradiation; a separate model differentiating between high and low radiation dose achieved AUC of 0.85 (95%CI: 0.74-0.96).
Conclusions: We conclude that serum miRNAs reflect radiation exposure and dose for humans undergoing TBI and may be used as functional biodosimeters for precise identification of people exposed to clinically significant radiation doses.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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