Identifying Urinary and Serum Exosome Biomarkers for Radiation Exposure Using a Data Dependent Acquisition and SWATH-MS Combined Workflow.
Identifying Urinary and Serum Exosome Biomarkers for Radiation Exposure Using a Data Dependent Acquisition and SWATH-MS Combined Workflow.
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DOI：
10.1016/j.ijrobp.2016.06.008
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发表时间：
2016-11-01
影响因子：
7
通讯作者：
Chen, Emily I.
中科院分区：
文献类型：
--
作者：
Kulkarni, Shilpa;Koller, Antonius;Mani, Kartik M.;Wen, Ruofeng;Alfieri, Alan;Saha, Subhrajit;Wang, Jian;Patel, Purvi;Bandeira, Nuno;Guha, Chandan;Chen, Emily I.
通过辐射反应生物标记物对辐射损伤进行早期和准确的评估是进行分类和早期干预的关键。尿液和血清等生物流体为此类分析提供了便利，最近的研究也表明，外切体是疾病进展过程中生物标志物的可靠来源。在这项研究中，我们分析了从尿液或血清中分离的尿总蛋白质组和外切体，以寻找致死性全身照射(WBI)小鼠急性和持续辐射损伤的潜在生物标志物。为了进行可行性研究，小鼠接受10.4GyWBI照射，在照射后24小时和72小时采集尿样和血清样本。通过LC-MS/MS工作流程分离和分析外切体，以获得辐射暴露特征。使用DDA和SWATH-MS相结合的工作流程方法来识别指示急性或持续辐射诱导反应的显著外体生物标记物。在验证研究中，小鼠暴露在3、6、8或10GyWBI中，并对样本进行分析以进行比较。尿总蛋白质组学和尿外切体蛋白质组学的比较表明，外切体蛋白质组学分析在识别辐射信号方面更具优势。可行性研究确定了23个来自尿液的生物标记物和24个来自血清外切体的生物标记物。尿外切体特征识别出与血清外切体不同的生理参数。尿液的外切体征表明肝脏、胃肠道和泌尿生殖道受损，而血清对辐射的反应显示血管损伤和急性炎症。在验证研究中，选定的尿外显体生物标记物在较低的辐射剂量下也显示出变化。外显体蛋白质组学揭示了WBI后依赖于辐射和时间的蛋白质特征。在尿液和血清中鉴定出47个差异分泌的蛋白质，这些数据表明了定义生物标志物来阐明高剂量电离辐射引起的组织相关和全身反应的可行性。这是第一次使用外显体蛋白质组学方法来鉴定辐射特征。
Early and accurate assessment of radiation injury by radiation-responsive biomarkers is critical for triage and early intervention. Biofluids such as urine and serum are convenient for such analysis, recent research also suggests that exosomes are a reliable source of biomarkers in disease progression. In this study, we analyzed total urine proteome, and exosomes isolated form urine or serum for potential biomarkers of acute and persistent radiation injury in mice exposed to lethal whole body irradiation (WBI). For feasibility studies, mice were irradiated at 10.4 Gy WBI, urine and serum samples were collected 24 and 72 hr post-irradiation. Exosomes were isolated and analyzed by LC-MS/MS- based workflow for radiation exposure signatures. A DDA and SWATH-MS combined workflow approach was used to identify significantly exosome biomarkers indicative of acute or persistent radiation-induced responses. For validation studies, mice were exposed to 3, 6, 8 or 10 Gy WBI and samples were analyzed for comparison. Comparison between total urine proteomics and urine exosome proteomics demonstrated that exosome proteomic analysis was superior in identifying radiation signatures. Feasibility studies identified 23 biomarkers from urine and 24 biomarkers from serum exosomes post-WBI. Urinary exosome signatures identified different physiological parameters than the ones obtained in serum exosomes. Exosome signatures from urine indicated injury of the liver, gastrointestinal, and genitourinary track, whereas serum showed vascular injuries and acute inflammation in response to radiation. Selected urinary exosomal biomarkers also showed changes at lower radiation doses in validation studies. Exosome proteomics revealed radiation- and time-dependent protein signatures after WBI. 47 differentially secreted proteins were identified in urinary and serum exosomes, together these data showed the feasibility of defining biomarkers that could elucidate tissue-associated and systemic response caused by high dose ionizing radiation. This is a first report employing exosome proteomics approach to identify radiation signatures.
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影响因子：
5.8
作者：
Pant S;Hilton H;Burczynski ME
通讯作者：
Burczynski ME
影响因子：
4.4
作者：
Sundgren, P. C.;Nagesh, V.;Elias, A.;Tsien, C.;Junck, L.;Hassan, D. M. Gomez;Lawrence, T. S.;Chenevert, T. L.;Rogers, L.;McKeever, P.;Cao, Y.
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Cao, Y.
影响因子：
3.3
作者：
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通讯作者：
Yang AJ
影响因子：
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作者：
Saha S;Bhanja P;Kabarriti R;Liu L;Alfieri AA;Guha C
通讯作者：
Guha C
影响因子：
13.6
作者：
Ling, Xuefeng B.;Sigdel, Tara K.;Sarwal, Minnie M.
通讯作者：
Sarwal, Minnie M.