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全血 RNA 生物标志物可预测非人类灵长类动物胸部放疗后的生存情况。

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

机构信息

Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, 10 Center Drive, Room B3B406, Bethesda, MD, 20892, USA.

出版信息

Sci Rep. 2024 Oct 3;14(1):22957. doi: 10.1038/s41598-024-72975-y.

DOI:10.1038/s41598-024-72975-y
PMID:39362942
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11449919/
Abstract

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.

摘要

辐射损伤,无论是来自放射治疗还是大规模伤亡事件,都需要一个能够有效地为患者分配资源的医疗保健系统。我们对接受上胸部辐射(9.8-10.7 Gy)的非人类灵长类动物模型的全血进行了全面的转录组分析。在多达 270 天的时间内,从辐射后多个时间点采集血液样本,初始时间点(第 3 天-第 40 天)至少有 n=6 个样本,共有 28 只灵长类动物。没有接受高剂量辐射的雄性动物存活到第 270 天。使用 R 中的弹性网络模型,我们发现与使用特定于单个日期的生物标志物相比,从第 3 天到第 21 天汇集生物标志物可提高我们辨别生存时间、胸腔积液或剂量的准确性。对于生存数据,在预测短期(少于 90 天)、中期(第 91-269 天)或长期(第 270 天)生存时,仅使用第 3 天数据的预测准确性为 0.14(95%置信区间(CI)为 0.1, 0.19),而男性和女性的汇总数据为 0.76(CI 为 0.69, 0.82)。当按生物学性别对汇总数据进行划分时,男性汇总数据的准确性为 0.7(CI 为 0.58, 0.8),女性汇总数据的准确性为 0.84(CI 为 0.76, 0.91)。作为辅助临床决策的工具,RNA 生物标志物的开发可以极大地改善辐射损伤患者的护理,无论是来自放射治疗还是大规模伤亡事件。进一步验证和临床转化这些发现可能会导致在辐射暴露的情况下改善患者护理和管理策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/b7f1dab677d9/41598_2024_72975_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/abd048817022/41598_2024_72975_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/f3d5bde16f39/41598_2024_72975_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/e07b190fbe39/41598_2024_72975_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/9cdd7153d635/41598_2024_72975_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/634bed78b472/41598_2024_72975_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/b7f1dab677d9/41598_2024_72975_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/abd048817022/41598_2024_72975_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/f3d5bde16f39/41598_2024_72975_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/e07b190fbe39/41598_2024_72975_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/9cdd7153d635/41598_2024_72975_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/634bed78b472/41598_2024_72975_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c283/11449919/b7f1dab677d9/41598_2024_72975_Fig6_HTML.jpg

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Extraction of high quality and high yield RNA from frozen EDTA blood.从冷冻 EDTA 血液中提取高质量、高产量的 RNA。
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