Abstract:BackgroundRapid dose assessment using biological dosimetry methods is essential to increase the chance of survival of exposed individuals in radiation accidents.ObjectivesWe compared the expression levels of the FDXR and RAD51 genes at 6 and 18 MV beam energies in human peripheral blood lymphocytes. The results of our study can be used to analyze radiation energy in biological dosimetry.MethodsFor this in vitro experimental study, from 36 students in the medical physics and virology departments, seven voluntar… Show more
“…When sensitivity is fixed at 100% in order to decrease the number of false negatives, although results differed, TNFSF4, FDXR and ZMAT3 still have a good performance score. Although ZMAT3 has been less studied, TNFSF4 and FDXR are known to be radiation-responsive and are often used in candidate gene approaches and validation panels [ 58 – 63 ]. Recently, a study provided an in vivo dose-response of the FDXR gene, both for very low doses or partial body exposure, showing good correlation between physically and biologically assessed doses, thus confirming the great potential of this gene as candidate radiation dosimetry biomarker [ 64 ].…”
PurposeTo 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.MethodsEligible 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.Results24 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.ConclusionGene 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.
“…When sensitivity is fixed at 100% in order to decrease the number of false negatives, although results differed, TNFSF4, FDXR and ZMAT3 still have a good performance score. Although ZMAT3 has been less studied, TNFSF4 and FDXR are known to be radiation-responsive and are often used in candidate gene approaches and validation panels [ 58 – 63 ]. Recently, a study provided an in vivo dose-response of the FDXR gene, both for very low doses or partial body exposure, showing good correlation between physically and biologically assessed doses, thus confirming the great potential of this gene as candidate radiation dosimetry biomarker [ 64 ].…”
PurposeTo 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.MethodsEligible 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.Results24 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.ConclusionGene 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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