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Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review

PURPOSE: To compile a list of genes that have been reported to be affected by external ionizing radiation (IR) and to assess their performance as candidate biomarkers for individual human radiation dosimetry. METHODS: Eligible studies were identified through extensive searches of the online database...

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Autores principales: Lacombe, Jerome, Sima, Chao, Amundson, Sally A., Zenhausern, Frederic
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991767/
https://www.ncbi.nlm.nih.gov/pubmed/29879226
http://dx.doi.org/10.1371/journal.pone.0198851
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author Lacombe, Jerome
Sima, Chao
Amundson, Sally A.
Zenhausern, Frederic
author_facet Lacombe, Jerome
Sima, Chao
Amundson, Sally A.
Zenhausern, Frederic
author_sort Lacombe, Jerome
collection PubMed
description PURPOSE: To compile a list of genes that have been reported to be affected by external ionizing radiation (IR) and to assess their performance as candidate biomarkers for individual human radiation dosimetry. METHODS: Eligible studies were identified through extensive searches of the online databases from 1978 to 2017. Original English-language publications of microarray studies assessing radiation-induced changes in gene expression levels in human blood after external IR were included. Genes identified in at least half of the selected studies were retained for bio-statistical analysis in order to evaluate their diagnostic ability. RESULTS: 24 studies met the criteria and were included in this study. Radiation-induced expression of 10,170 unique genes was identified and the 31 genes that have been identified in at least 50% of studies (12/24 studies) were selected for diagnostic power analysis. Twenty-seven genes showed a significant Spearman’s correlation with radiation dose. Individually, TNFSF4, FDXR, MYC, ZMAT3 and GADD45A provided the best discrimination of radiation dose < 2 Gy and dose ≥ 2 Gy according to according to their maximized Youden’s index (0.67, 0.55, 0.55, 0.55 and 0.53 respectively). Moreover, 12 combinations of three genes display an area under the Receiver Operating Curve (ROC) curve (AUC) = 1 reinforcing the concept of biomarker combinations instead of looking for an ideal and unique biomarker. CONCLUSION: Gene expression is a promising approach for radiation dosimetry assessment. A list of robust candidate biomarkers has been identified from analysis of the studies published to date, confirming for example the potential of well-known genes such as FDXR and TNFSF4 or highlighting other promising gene such as ZMAT3. However, heterogeneity in protocols and analysis methods will require additional studies to confirm these results.
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spelling pubmed-59917672018-06-15 Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review Lacombe, Jerome Sima, Chao Amundson, Sally A. Zenhausern, Frederic PLoS One Research Article PURPOSE: To compile a list of genes that have been reported to be affected by external ionizing radiation (IR) and to assess their performance as candidate biomarkers for individual human radiation dosimetry. METHODS: Eligible studies were identified through extensive searches of the online databases from 1978 to 2017. Original English-language publications of microarray studies assessing radiation-induced changes in gene expression levels in human blood after external IR were included. Genes identified in at least half of the selected studies were retained for bio-statistical analysis in order to evaluate their diagnostic ability. RESULTS: 24 studies met the criteria and were included in this study. Radiation-induced expression of 10,170 unique genes was identified and the 31 genes that have been identified in at least 50% of studies (12/24 studies) were selected for diagnostic power analysis. Twenty-seven genes showed a significant Spearman’s correlation with radiation dose. Individually, TNFSF4, FDXR, MYC, ZMAT3 and GADD45A provided the best discrimination of radiation dose < 2 Gy and dose ≥ 2 Gy according to according to their maximized Youden’s index (0.67, 0.55, 0.55, 0.55 and 0.53 respectively). Moreover, 12 combinations of three genes display an area under the Receiver Operating Curve (ROC) curve (AUC) = 1 reinforcing the concept of biomarker combinations instead of looking for an ideal and unique biomarker. CONCLUSION: Gene expression is a promising approach for radiation dosimetry assessment. A list of robust candidate biomarkers has been identified from analysis of the studies published to date, confirming for example the potential of well-known genes such as FDXR and TNFSF4 or highlighting other promising gene such as ZMAT3. However, heterogeneity in protocols and analysis methods will require additional studies to confirm these results. Public Library of Science 2018-06-07 /pmc/articles/PMC5991767/ /pubmed/29879226 http://dx.doi.org/10.1371/journal.pone.0198851 Text en © 2018 Lacombe et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lacombe, Jerome
Sima, Chao
Amundson, Sally A.
Zenhausern, Frederic
Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review
title Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review
title_full Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review
title_fullStr Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review
title_full_unstemmed Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review
title_short Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review
title_sort candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: a systematic review
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991767/
https://www.ncbi.nlm.nih.gov/pubmed/29879226
http://dx.doi.org/10.1371/journal.pone.0198851
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