Whole-blood RNA biomarkers for predicting survival in non-human primates following thoracic radiation

Radiation injury, either from radiotherapy or a mass-casualty event requires a health care system that can efficiently allocate resources to patients. We conducted a comprehensive transcriptome analysis of whole blood from a nonhuman primate model that received upper thoracic radiation (9.8-10.7 Gy). Blood samples were collected at multiple time points, extending up to 270 days post-irradiation with a minimum n = 6 for initial time points (Day 3-Day 40) and a total number of n = 28 primates. No males receiving the higher dose survived to Day 270. Using the Elastic Net model in R we found that pooling biomarkers from Day 3-21 increased our accuracy in discerning survival time, pleural effusion or dose compared to using biomarkers specific to a single day. For survival data, in predicting short term (less than 90 day), medium term (Day 91-269) or long-term survival (Day 270), prediction accuracy using only Day 3 data was 0.14 (95% Confidence Interval (CI) 0.1, 0.19) while pooled data for Male and Female was 0.76 (CI 0.69, 0.82). When pooled data was divided by biological sex, accuracy was 0.7 (CI 0.58, 0.8) for pooled data from Males and 0.84 (CI 0.76, 0.91) for Females. The development of RNA biomarkers as a tool to aid in clinical decision-making could significantly improve patient care in cases of radiation injury, whether from radiotherapy or mass-casualty events. Further validation and clinical translation of these findings could lead to improved patient care and management strategies in cases of radiation exposure.