Jovanović Nikola, Mitrović Tatjana, Cvetković Vladimir J, Tošić Svetlana, Vitorović Jelena, Stamenković Slaviša, Nikolov Vesna, Kostić Aleksandar, Vidović Nataša, Krstić Miljan, Jevtović-Stoimenov Tatjana, Pavlović Dušica
University of Niš, Department of Biology and Ecology, Faculty of Sciences and Mathematics, 18000 Niš, Serbia.
University of Niš, Faculty of Medicine, Clinic of Neurosurgery, Clinical Center, 18000 Niš, Serbia.
Medicina (Kaunas). 2019 Feb 1;55(2):34. doi: 10.3390/medicina55020034.
Despite recent advances in treatment, glioblastoma (GBM) remains the most lethal and aggressive brain tumor. A continuous search for a reliable molecular marker establishes the methylation status of the O6-methylguanine-DNA methyltransferase () gene promoter as a key prognostic factor in primary glioblastoma. The aim of our study was to screen Serbian patients with primary glioblastoma for an promoter hypermethylation and to evaluate its associations with overall survival (OS) and sensitivity to temozolomide (TMZ) treatment. A cohort of 30 Serbian primary glioblastoma patients treated with radiation therapy and chemotherapy were analyzed for promoter methylation and correlated with clinical data. methylation status was determined in 25 out of 30 primary glioblastomas by methylation-specific PCR (MSP). promoter hypermethylation was detected in 12 out of 25 patients (48%). The level of promoter methylation did not correlate with patients' gender ( = 0.409), age ( = 0.536), and OS ( = 0.394). Treatment with TMZ significantly prolonged the median survival of a patient (from 5 to 15 months; < 0.001). Due to a small cohort of primary GBM patients, our study is not sufficient for definitive conclusions regarding the prognostic value of methylation for the Serbian population. Our preliminary data suggest a lack of association between promoter methylation and overall survival and a significant correlation of TMZ treatment with overall survival. Further population-based studies are needed to assess the prognostic value of the promoter methylation status for patients with primary glioblastoma.
尽管近年来治疗方法有所进步，但胶质母细胞瘤（GBM）仍然是最致命且侵袭性最强的脑肿瘤。持续寻找可靠的分子标志物确定了O6-甲基鸟嘌呤-DNA甲基转移酶（）基因启动子的甲基化状态是原发性胶质母细胞瘤的关键预后因素。我们研究的目的是筛查塞尔维亚原发性胶质母细胞瘤患者的启动子高甲基化情况，并评估其与总生存期（OS）以及对替莫唑胺（TMZ）治疗敏感性的相关性。对30例接受放疗和化疗的塞尔维亚原发性胶质母细胞瘤患者进行队列分析，检测启动子甲基化情况并与临床数据相关联。通过甲基化特异性PCR（MSP）在30例原发性胶质母细胞瘤中的25例中确定了甲基化状态。在25例患者中的12例（48%）检测到启动子高甲基化。启动子甲基化水平与患者的性别（=0.409）、年龄（=0.536）和总生存期（=0.394）均无相关性。TMZ治疗显著延长了患者的中位生存期（从5个月延长至15个月；<0.001）。由于原发性GBM患者队列较小，我们的研究不足以就甲基化对塞尔维亚人群的预后价值得出确定性结论。我们的初步数据表明启动子甲基化与总生存期之间缺乏关联，而TMZ治疗与总生存期存在显著相关性。需要进一步开展基于人群的研究来评估启动子甲基化状态对原发性胶质母细胞瘤患者的预后价值。
