Gene expression signatures of radiation response are specific, durable and accurate in mice and humans.
BACKGROUND
Previous work has demonstrated the potential for peripheral blood (PB) gene expression profiling for the detection of disease or environmental exposures.


RESULTS
We have sought to determine the impact of several variables on the PB gene expression profile of an environmental exposure, ionizing radiation, and to determine the specificity of the PB signature of radiation versus other genotoxic stresses. Neither genotype differences nor the time of PB sampling caused any lessening of the accuracy of PB signatures to predict radiation exposure, but sex difference did influence the accuracy of the prediction of radiation exposure at the lowest level (50 cGy). A PB signature of sepsis was also generated and both the PB signature of radiation and the PB signature of sepsis were found to be 100% specific at distinguishing irradiated from septic animals. We also identified human PB signatures of radiation exposure and chemotherapy treatment which distinguished irradiated patients and chemotherapy-treated individuals within a heterogeneous population with accuracies of 90% and 81%, respectively.


CONCLUSIONS
We conclude that PB gene expression profiles can be identified in mice and humans that are accurate in predicting medical conditions, are specific to each condition and remain highly accurate over time.
Meadows
Sarah K
SK
Division of Cellular Therapy, Duke University Medical Center, Durham, North Carolina, United States of America.
Dressman
Holly K
HK
Muramoto
Garrett G
GG
Himburg
Heather
H
Salter
Alice
A
Wei
ZhengZheng
Z
Ginsburg
Geoffrey S
GS
Ginsburg
Geoff
G
Chao
Nelson J
NJ
Nevins
Joseph R
JR
Chute
John P
JP
D000818:Animals; D004731:Endotoxins / Q000378:metabolism; D004781:Environmental Exposure; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D015203:Reproducibility of Results
D004731:Endotoxins; D008070:Lipopolysaccharides