Determination of global DNA methylation level by methylation-sensitive comet assay in patients with urinary bladder cancer.

IF 2.5 4区医学 Q3 GENETICS & HEREDITY Mutagenesis Pub Date : 2024-08-10 DOI:10.1093/mutage/geae018

Özer Koçak, Selin Kankaya, Göktuğ Kalender, Sinharib Citgez, Bülent Önal, Yıldız Dinçer

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Abstract

DNA methylation is an important mechanism in the regulation of gene expression and maintenance of genomic integrity. Aberrant DNA methylation is an early event in carcinogenesis. DNA methyltransferase inhibitors are used to restore aberrant DNA methylation and inhibit tumor growth. Evaluation of DNA methylation level is important for an effective anti-cancer therapy. In the present study, the determination of global DNA methylation levels in patients with urinary bladder cancer was proposed. The methylation-sensitive comet assay determined the global DNA methylation level at the level of single cells. McrBC enzyme, a methylation-sensitive restriction endonuclease was used for enzymatic digestion to generate additional breaks at methylated sites. % DNA methylation level was significantly higher in patients with bladder cancer compared to the control group. The clinical performance of % DNA methylation analysis by methylation-sensitive comet assay was evaluated by ROC curve. Using the cut-off value of 6,5% DNA methylation, 92% sensitivity, and 42% specificity were obtained. In conclusion, global DNA methylation measured by methylation-sensitive comet assay may be a promising non-invasive biomarker that reduces interventional tests required in the diagnosis and follow-up of urinary bladder cancer.

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用甲基化敏感彗星测定法确定膀胱癌患者的 DNA 整体甲基化水平

DNA 甲基化是调控基因表达和维护基因组完整性的重要机制。异常的 DNA 甲基化是致癌的早期事件。DNA 甲基转移酶抑制剂可用于恢复异常的 DNA 甲基化，抑制肿瘤生长。评估 DNA 甲基化水平对有效抗癌治疗非常重要。本研究提出了测定膀胱癌患者DNA甲基化水平的方法。甲基化敏感彗星测定法可在单细胞水平上确定全球 DNA 甲基化水平。使用甲基化敏感限制性内切酶 McrBC 进行酶解，在甲基化位点产生额外的断裂。与对照组相比，膀胱癌患者的 DNA 甲基化率水平明显较高。采用甲基化敏感彗星分析法进行的 DNA 甲基化率分析的临床表现以 ROC 曲线进行评估。以 6.5% 的 DNA 甲基化率为临界值，灵敏度为 92%，特异度为 42%。总之，用甲基化敏感彗星测定法测量全局 DNA 甲基化可能是一种很有前途的非侵入性生物标志物，可减少膀胱癌诊断和随访过程中所需的介入性检测。

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来源期刊

Mutagenesis 生物-毒理学

CiteScore

5.90

自引率

3.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.