Kopcalic Katarina, Petrovic Nina, Stanojkovic Tatjana P, Stankovic Vesna, Bukumiric Zoran, Roganovic Jelena, Malisic Emina, Nikitovic Marina
Institute for Oncology and Radiology of Serbia, Department of Radiation Oncology, Belgrade, Serbia.
Institute for Oncology and Radiology of Serbia, Department for Experimental Oncology, Belgrade, Serbia; University of Belgrade, Vinca Institute of Nuclear Sciences, Department of Radiobiology and Molecular Genetics, Belgrade, Serbia.
Pathol Res Pract. 2019 Apr;215(4):626-631. doi: 10.1016/j.prp.2018.12.007. Epub 2018 Dec 10.
Nearly sixty percent of patients with prostate cancer (PCa) undergo radiation therapy (RT). During the course of treatment patients may experience normal tissue reactions. It is a well established fact that genetic and epigenetic mechanisms, such as microRNA (miRNA) level changes might be associated with radiotoxicity, as a response to irradiation.
This is the first study that has investigated levels of radiosensory miRNAs in association with acute genitourinary radiotoxicity extracted from peripheral blood mononuclear cells (PBCs), in three points; before RT (BRT), after RT (ART) and on the first control examination (FCONT). We measured levels of miR-21/146a/155 expression by quantitative real-time PCR (qRT-PCR), comparative ΔΔCt method, in fifteen patients with localized prostate cancer, treated with three-dimensional conformal radiotherapy (3DCRT). Nine subjects have experienced acute genitourinary (GU) radiotoxicity whereas six where without GU radiotoxicity.
Firstly, we detected the highest levels of miR-21 in ART group (p = 0.043) in the patients with acute GU radiotoxicity. Secondly, we found trend towards higher miR-21 levels and significantly higher levels of miR-146a/155 within the patients with acute GU toxicity than in patients without (p = 0.068, p = 0.016, and p = 0.010, respectively). Thirdly, we detected significant change in miR-146a/155 levels within the patients without acute GU radiotoxicity during RT p = 0.042, and p = 0.041, respectively).
miR-21/146a/155 might be useful potential factors of radiosensitivity and acute genitourinary radiotoxicity in prostate cancer patients. miRNA might have great potential as predictors of various pathological conditions extracted from PBMCs.
近60%的前列腺癌(PCa)患者接受放射治疗(RT)。在治疗过程中,患者可能会出现正常组织反应。遗传和表观遗传机制,如微小RNA(miRNA)水平变化可能与放射毒性相关,这是对辐射的一种反应,这是一个已被充分证实的事实。
这是第一项研究,在三个时间点,即放疗前(BRT)、放疗后(ART)和首次对照检查时(FCONT),研究了从外周血单核细胞(PBC)中提取的与急性泌尿生殖系统放射毒性相关的放射感应性miRNA水平。我们通过定量实时聚合酶链反应(qRT-PCR)、比较ΔΔCt法,测量了15例接受三维适形放疗(3DCRT)的局限性前列腺癌患者中miR-21/146a/155的表达水平。9名受试者经历了急性泌尿生殖系统(GU)放射毒性,而6名受试者没有GU放射毒性。
首先,我们在有急性GU放射毒性的患者的ART组中检测到miR-21的最高水平(p = 0.043)。其次,我们发现,有急性GU毒性的患者体内miR-21水平有升高趋势,miR-146a/155水平明显高于无急性GU毒性的患者(分别为p = 0.068、p = 0.016和p = 0.010)。第三,我们在无急性GU放射毒性的患者放疗期间检测到miR-146a/155水平有显著变化(分别为p = 0.042和p = 0.041)。
miR-21/146a/155可能是前列腺癌患者放射敏感性和急性泌尿生殖系统放射毒性的潜在有用因素。miRNA作为从PBMC中提取的各种病理状况的预测指标可能具有巨大潜力。