Manning Grainne, Tichý Aleš, Sirák Igor, Badie Christophe
Cancer Mechanisms and Biomarkers Group, Centre for Radiation, Chemical and Environmental Hazards, Radiation Effects Department, Public Health England, Oxfordshire, UK.
Department of Radiobiology, Faculty of Military Health Sciences in Hradec Králové, University of Defence, Brno, Czechia.
Front Immunol. 2017 Apr 10;8:412. doi: 10.3389/fimmu.2017.00412. eCollection 2017.
Ionizing radiation (IR) exposure of cells and triggers a complex cellular response among which modifications of gene expression have been consistently reported. Nevertheless, little is currently known about the transcriptionally responsive genes which play a role in the inflammation response. In order to improve our understanding of such transcriptional response to radiation , we simultaneously monitored the expression of 249 genes associated with the inflammation response over the course of the radiotherapy treatment in blood of patients treated for endometrial or head and neck cancer. We have identified genes whose transcriptional expression is either upregulated () or downregulated () several fold . These modifications were consistently detected across patients and further confirmed by quantitative real-time polymerase chain reaction (QRT-PCR); they were specifically significant toward the end of the radiotherapy treatment, 5 weeks following the first radiation fraction and more pronounced in endometrial patients (respectively, 2.9, 4.1, and 1.8 times). Importantly, in an attempt to correlate expression levels with normal tissue reaction to IR, we also identified three other genes , and whose expression level fluctuations during radiotherapy were more pronounced in patients developing late normal tissue responses to curative radiotherapy after the end of the radiotherapy treatment. Overall, we identified inflammation-associated genes which are promising biomarkers of IR exposure and susceptibility to radiation-induced toxicity.
细胞受到电离辐射(IR)照射会引发复杂的细胞反应,其中基因表达的改变一直有报道。然而,目前对于在炎症反应中起作用的转录反应基因知之甚少。为了更好地理解这种对辐射的转录反应,我们在子宫内膜癌或头颈癌患者放疗过程中,同时监测了血液中与炎症反应相关的249个基因的表达。我们鉴定出了转录表达上调()或下调()数倍的基因。这些改变在患者中一致被检测到,并通过定量实时聚合酶链反应(QRT-PCR)进一步证实;它们在放疗接近尾声时,即首次放疗剂量后的5周时尤为显著,且在子宫内膜癌患者中更为明显(分别为2.9倍、4.1倍和1.8倍)。重要的是,为了将表达水平与正常组织对IR的反应相关联,我们还鉴定出另外三个基因,并且在放疗结束后对根治性放疗出现晚期正常组织反应的患者中,这三个基因在放疗期间的表达水平波动更为明显。总体而言,我们鉴定出了与炎症相关的基因,它们有望成为IR暴露和辐射诱导毒性易感性的生物标志物。