Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), Lahore, Pakistan.
Department of Medical Oncology, SKMCH&RC, Lahore, Pakistan.
Mol Biol Rep. 2024 Mar 23;51(1):433. doi: 10.1007/s11033-024-09363-2.
Glioblastoma multiforme (GBM), the most prevalent subgroup of neuroepithelial tumors, is characterized by dismal overall survival (OS). Several studies have linked O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation to OS in GBM patients. However, MGMT methylation frequencies vary geographically and across ethnicities, with limited data for South Asian populations, including Pakistan. This study aimed to analyze MGMT promoter methylation in Pakistani GBM patients.
Consecutive primary GBM patients diagnosed ≥ 18 years-of-age, with no prior chemotherapy or radiotherapy history, were retrospectively selected. DNA was isolated from formalin-fixed-paraffin-embedded tissues. MGMT promoter methylation was analyzed using methylation-specific PCR. Clinical, pathological, and treatment data were assessed using Fisher's exact/Chi-squared tests. OS was calculated using Kaplan-Meier analysis in SPSS 27.0.1.
The study included 48 GBM patients, comprising 38 (79.2%) males and 10 (20.8%) females. The median diagnosis age was 49.5 years (range 18-70). MGMT methylation was observed in 87.5% (42/48) of all cases. Patients with MGMT methylation undergoing radiotherapy or radiotherapy plus chemotherapy exhibited significantly improved median OS of 7.2 months (95% CI, 3.7-10.7; P < 0.001) and 16.9 months (95% CI, 15.9-17.9; P < 0.001), respectively, compared to those undergoing surgical resection only (OS: 2.2 months, 95% CI, 0.8-3.6).
This is the first comprehensive study highlighting a predominance of MGMT methylation in Pakistani GBM patients. Furthermore, our findings underscore the association of MGMT methylation with improved OS across diverse treatment modalities. Larger studies are imperative to validate our findings for better management of Pakistani GBM patients.
多形性胶质母细胞瘤（GBM）是神经上皮肿瘤中最常见的亚组，其总体生存（OS）较差。几项研究将 O6-甲基鸟嘌呤-DNA-甲基转移酶（MGMT）启动子甲基化与 GBM 患者的 OS 联系起来。然而，MGMT 甲基化频率在地理上和种族上存在差异，南亚人群，包括巴基斯坦的数据有限。本研究旨在分析巴基斯坦 GBM 患者的 MGMT 启动子甲基化。
回顾性选择连续诊断为≥18 岁、无先前化疗或放疗史的原发性 GBM 患者。从福尔马林固定石蜡包埋组织中分离 DNA。使用甲基化特异性 PCR 分析 MGMT 启动子甲基化。使用 Fisher's exact/Chi-squared 检验评估临床、病理和治疗数据。使用 SPSS 27.0.1 中的 Kaplan-Meier 分析计算 OS。
该研究纳入了 48 名 GBM 患者，其中 38 名（79.2%）为男性，10 名（20.8%）为女性。中位诊断年龄为 49.5 岁（范围 18-70 岁）。所有病例中观察到 87.5%（42/48）的 MGMT 甲基化。接受放疗或放疗加化疗的 MGMT 甲基化患者中位 OS 分别显著提高至 7.2 个月（95%CI，3.7-10.7；P<0.001）和 16.9 个月（95%CI，15.9-17.9；P<0.001），而仅接受手术切除的患者 OS 为 2.2 个月（95%CI，0.8-3.6）。
这是第一项强调巴基斯坦 GBM 患者中 MGMT 甲基化占主导地位的综合研究。此外，我们的研究结果强调了 MGMT 甲基化与不同治疗方式下 OS 改善的相关性。更大规模的研究对于验证我们的发现以更好地管理巴基斯坦 GBM 患者至关重要。
