Screening Of Radiation Biomarkers And Dose Prediction At High And Low Dose Rate

When an organism is subjected to ionizing radiation,some special events or changes that occur at the level of biochemistry,molecules,cells,tissues,or organs are called radiation biomarkers.Generally,the change of biomarkers is proportional to radiation dose,which can be used to assess the radiation dose received by the individual and provide a scientific basis for radiation risk assessment.When a large-scale accident occurs,there are usually both high and low dose rate radiation.At present,most researches on radiation biomarkers have focused on high dose rate(high dose rate,HDR)conditions,while the researches on low dose rate(low dose rate,LDR)conditions are relatively lacking.In order to provide fast and accurate dose prediction and clinical diagnosis methods in the event of large-scale radioactive accident,and to provide a more complete theoretical basis for radiation risk assessment,this subject intends to carry out the screening and dose prediction of radiation biomarkers under high and low dose rate conditions.Based on the gene expression profile data of human peripheral blood irradiated by X-rays under high and low dose rate conditions,the differentially expressed genes were screened by single factor analysis of variance.The selected genes were enriched in biological pathway analysis,and the genes in biological pathways with significant differences were analyzed by multiple linear regression,one can establish the optimal radiation dose prediction model under the conditions of high and low dose rate.The results showed that through enrichment analysis of differentially expressed genes under HDR conditions,we obtained 9 KEGG pathways,including nucleotide excision repair pathway,cytokine and cytokine receptor interaction pathway,FoxO signaling pathway,cell cycle,and so on.The differentially expressed genes under LDR enriched 11 pathways,including fructose and mannose metabolic pathways,cytokine-cytokine receptor interaction pathways,HIF-1 signaling pathway,and FoxO signaling pathway.Through multiple linear regression analysis of genes in each pathway,we finally determined 9 pathways under HDR conditions and 10 pathways except fructose and mannose metabolism pathways under LDR conditions.The genes in these pathways were used as radiation biomarkers to establish a radiation dose prediction model.Spearman correlation analysis was also conducted on differentially expressed genes at high and low dose rates,and the eligible genes were screened out.The protein interaction analysis was performed on these genes,and high dose rates were screened based on the number of protein interaction nodes.Under the conditions,13 genes such as PCNA,ESR1 and CDKN1A were used as radiation biomarkers;under low dose rate conditions,a total of 16 genes such as PCNA,MDM2 and GRM2 were screened as radiation biomarkers.Finally,through the screening of biomarkers of radiation,a radiation dose prediction model under high and low dose rate conditions was established.According to the research,there are obvious differences in radiation biomarkers used for dose prediction under high and low dose rate conditions,so it is necessary to distinguish the dose rate in the research of radiation biomarker;multiple genes selected at high and low dose rates can be used as potential radiation biomarkers;the established dose prediction model has a relatively reliable prediction effect,and has potential application value for risk assessment and medical decision-making when large-scale radioactive accidents occur.