Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
Int J Radiat Oncol Biol Phys. 2015 Aug 1;92(5):1108-1115. doi: 10.1016/j.ijrobp.2015.03.040. Epub 2015 Apr 7.
Ionizing radiation affects the proteome of irradiated cells and tissue, yet data concerning changes induced during radiation therapy (RT) in human blood are fragmentary and inconclusive. We aimed to identify features of serum proteome and associated processes involved in response to partial body irradiation during cancer treatment.
Twenty patients with head and neck squamous cell cancer (HNSCC) and 20 patients with prostate cancer received definitive intensity modulated RT. Blood samples were collected before RT, just after RT, and 1 month after the end of RT. Complete serum proteome was analyzed in individual samples, using a shotgun liquid chromatography-tandem mass spectrometry approach which allowed identification of approximately 450 proteins. Approximately 100 unique proteins were quantified in all samples after exclusion of immunoglobulins, and statistical significance of differences among consecutive samples was assessed. Processes associated with quantified proteins and their functional interactions were predicted using gene ontology tools.
RT-induced changes were marked in the HNSCC patient group: 22 upregulated and 33 downregulated proteins were detected in post-RT sera. Most of the changes reversed during follow-up, yet levels of some proteins remained affected 1 month after the end of RT. RT-upregulated proteins were associated with acute phase, inflammatory response, and complement activation. RT-downregulated proteins were associated with transport and metabolism of lipids (plasma apolipoproteins) and blood coagulation. RT-induced changes were much weaker in prostate cancer patients, which corresponded to differences in acute radiation toxicity observed in both groups. Nevertheless, general patterns of RT-induced sera proteome changes were similar in both of the groups of cancer patients.
In this pilot study, we proposed to identify a molecular signature of radiation response, based on specific features of serum proteome. The signature included upregulation of factors involved in acute or inflammatory response but also downregulation of plasma apolipoproteins and factors involved in blood coagulation.
电离辐射会影响受照射细胞和组织的蛋白质组，然而关于在人类血液中放射治疗（RT）期间诱导的变化的数据是零碎的且不确定的。我们旨在鉴定血清蛋白质组的特征以及与癌症治疗期间部分身体照射反应相关的过程。
20 例头颈部鳞状细胞癌（HNSCC）和 20 例前列腺癌患者接受了根治性调强 RT。在 RT 前、RT 后即刻和 RT 结束后 1 个月采集血液样本。使用 shotgun 液相色谱-串联质谱法（shotgun liquid chromatography-tandem mass spectrometry approach）在单个样本中分析完整的血清蛋白质组，该方法允许鉴定大约 450 种蛋白质。在排除免疫球蛋白后，对所有样本中约 100 种独特的蛋白质进行了定量，评估了连续样本之间差异的统计学意义。使用基因本体论工具预测与定量蛋白质相关的过程及其功能相互作用。
RT 诱导的变化在 HNSCC 患者组中很明显：在 RT 后血清中检测到 22 种上调和 33 种下调的蛋白质。大多数变化在随访期间逆转，但一些蛋白质的水平在 RT 结束后 1 个月仍受影响。RT 上调的蛋白质与急性期、炎症反应和补体激活有关。RT 下调的蛋白质与脂质（血浆载脂蛋白）和血液凝固的运输和代谢有关。前列腺癌患者的 RT 诱导变化要弱得多，这与两组观察到的急性放射毒性差异相对应。然而，在两组癌症患者中，RT 诱导的血清蛋白质组变化的总体模式是相似的。
在这项初步研究中，我们提出了基于血清蛋白质组特定特征来识别放射反应分子特征的方法。该特征包括参与急性期或炎症反应的因子的上调，但也包括血浆载脂蛋白和参与血液凝固的因子的下调。
