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Abstract：
The O-6-methylguanine-DNA methyltransferase (MGMT) gene is a critical guardian of genomic integrity. MGMT methylation in diffuse gliomas serves as an important determinant of patients\' prognostic outcomes, more specifically in glioblastomas (GBMs). In GBMs, the absence of MGMT methylation, known as MGMT promoter unmethylation, often translates into a more challenging clinical scenario, tending to present resistance to chemotherapy and a worse prognosis. A pyrosequencing (PSQ) technique was used to analyze MGMT methylation status at different cut-offs (5%, 9%, and 11%) in a sample of 78 patients diagnosed with IDH-wildtype grade 4 GBM. A retrospective analysis was provided to collect clinicopathological and prognostic data. A statistical analysis was used to establish an association between methylation status and treatment response (TR) and disease-specific survival (DSS). The patients with methylated MGMT status experienced progressive disease rates of 84.6%, 80%, and 78.4% at the respective cut-offs of 5%, 9%, and 11%. The number was considerably higher when considering unmethylated patients, as all patients (100%), regardless of the cut-off, presented progressive disease. Regarding disease-specific survival (DSS), the Hazard Ratio (HR) was HR = 0.74 (0.45-1.24; p = 0.251); HR = 0.82 (0.51-1.33; p = 0.425); and HR = 0.79 (0.49-1.29; p = 0.350), respectively. Our study concludes that there is an association between MGMT unmethylation and worse TR and DSS. The 9% cut-off demonstrated a greater potential for patient survival as a function of time, which may shed light on the future need for standardization of MGMT methylation positivity parameters in PSQ.
摘要：
O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）基因是基因组完整性的关键监护人。弥漫性胶质瘤中MGMT甲基化是患者预后结果的重要决定因素，更具体地在胶质母细胞瘤（GBM）。在GBM中,缺乏MGMT甲基化，称为MGMT启动子非甲基化，通常会转化为更具挑战性的临床场景，倾向于对化疗产生耐药性，预后较差。焦磷酸测序（PSQ）技术用于分析不同截止条件下的MGMT甲基化状态（5％，9%,和11％）在78例诊断为IDH野生型4GBM的患者样本中。提供回顾性分析以收集临床病理和预后数据。使用统计分析来建立甲基化状态与治疗反应(TR)和疾病特异性存活(DSS)之间的关联。甲基化MGMT状态的患者病情进展率为84.6%，80%,和78.4%，分别为5%的截止值，9%,和11%。考虑到非甲基化患者的人数要高得多，作为所有患者（100％），不管切断了，呈现进行性疾病。关于疾病特异性生存率（DSS），危险比（HR）为HR=0.74（0.45-1.24；p=0.251）；HR=0.82（0.51-1.33；p=0.425）；HR=0.79（0.49-1.29；p=0.350），分别。我们的研究得出结论，MGMT未甲基化与更差的TR和DSS之间存在关联。9％的截止值表明，随着时间的变化，患者的生存潜力更大。这可能揭示了PSQ中MGMT甲基化阳性参数标准化的未来需求。
