Clinical role of NDRG2-based methylation status on survival pattern of glioblastoma

Menha Swellam, Mohamed K. Khalifa, Amira M Nageeb, Lobna Ezz El-Arab, Manal El-Mahdy, Khaled El-Bahy, Magda Sayed Mahmoud
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Abstract

Objectives: Gliobalstoma is the most common primary brain tumor in adults with an extensive genetic and transcriptional heterogeneity, still identification of the role of DNA methylation, as one of epigenetic alterations, is emerged. Authors aimed to study the clinical role of N-myc downstream-regulated gene 2 (NDRG2) –based methylation among GBM patients versus benign neurological diseases (BND), investigate its prognostic role and its relation with survival outcomes. Methods: A total of 78 FFPE specimens were recruited as follows: GBM ( n = 58) and BND ( n = 20) then analyzed for NDRG2 methylation using Methyl II quantitative PCR system. The sensitivity and specificity of methylation was detected using receiver operating characteristic (ROC) curve and the relation with clinicopathological criteria for GBM and response to treatment were studied. Survival patterns; progression free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier analyses. Results: Mean methylation NDRG2 level was significantly increased in GBM patients as compared to BND and its sensitivity and specificity were 96.55% and 95%, respectively with area under curve (AUC) equals 0.973. Among the clinical characteristic factors, mean methylation level reported significant difference with ECOG and tumor site. Survival out comes revealed that NDRG2 methylation increased with worse PFS and OS at significant level (long rank test X 2 = 13.3, p < .0001; and X 2 = 7.1, p = .008, respectively). Conclusion: Current findings highlight the importance of studying DNA methylation of NDRG2 as a key factor to understand the role of epigenetic alterations in GBM.
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基于 NDRG2 的甲基化状态对胶质母细胞瘤生存模式的临床作用
研究目的胶质母细胞瘤是成人中最常见的原发性脑肿瘤,具有广泛的遗传和转录异质性,而DNA甲基化作为表观遗传学改变之一,其作用仍有待鉴定。作者旨在研究基于 N-myc 下游调控基因 2(NDRG2)的甲基化在 GBM 患者与良性神经系统疾病(BND)患者中的临床作用,调查其预后作用及其与生存结果的关系。研究方法共收集了 78 份 FFPE 标本,具体如下:然后使用 Methyl II 定量 PCR 系统分析 NDRG2 甲基化。利用接收器操作特征曲线(ROC)检测甲基化的敏感性和特异性,并研究甲基化与 GBM 临床病理标准和治疗反应的关系。采用卡普兰-梅耶分析法对生存模式、无进展生存期(PFS)和总生存期(OS)进行了分析。结果与BND相比,GBM患者的平均甲基化NDRG2水平明显升高,其敏感性和特异性分别为96.55%和95%,曲线下面积(AUC)等于0.973。在临床特征因素中,平均甲基化水平与 ECOG 和肿瘤部位有显著差异。存活率结果显示,NDRG2甲基化水平的增加与较差的PFS和OS有显著关系(长秩检验X 2 = 13.3,p < .0001;X 2 = 7.1,p = .008)。结论目前的研究结果凸显了研究 NDRG2 DNA 甲基化的重要性,这是了解表观遗传学改变在 GBM 中的作用的关键因素。
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来源期刊
CiteScore
4.00
自引率
0.00%
发文量
88
审稿时长
15 weeks
期刊介绍: International Journal of Immunopathology and Pharmacology is an Open Access peer-reviewed journal publishing original papers describing research in the fields of immunology, pathology and pharmacology. The intention is that the journal should reflect both the experimental and clinical aspects of immunology as well as advances in the understanding of the pathology and pharmacology of the immune system.
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