The predictive but not prognostic value of MGMT promoter methylation status in elderly glioblastoma patients: a meta-analysis.
The predictive but not prognostic value of MGMT promoter methylation status in elderly glioblastoma patients: a meta-analysis.
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老年胶质母细胞瘤患者 MGMT 启动子甲基化状态的预测而非预后价值：荟萃分析
DOI：
10.1371/journal.pone.0085102
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Yin AA;Zhang LH;Cheng JX;Dong Y;Liu BL;Han N;Zhang X
背景o6 -甲基鸟嘌呤- dna甲基转移酶（MGMT）启动子状态在老年胶质母细胞瘤患者中的临床意义尚不明确。在此，我们报告了一项荟萃分析，以寻求其在该亚群中临床相关性的有效证据。方法系统检索PubMed、EMBASE和Cochrane数据库的相关文献。研究MGMT启动子状态与老年患者（≥65岁）生存数据之间关系的研究符合入选条件。结果共纳入16项研究，其中13项纳入最终分析。老年患者MGMT启动子甲基化的总比例为47%(95%置信区间[CI]: 42-52%)，与年轻患者相似。分析显示，根据指定的治疗方法，MGMT状态对老年患者总生存（OS）的不同影响：甲基化与未甲基化：(1)含替莫唑胺（TMZ）的治疗：风险比[HR] 0.49, 95% CI 0.41-0.58；(2)无tmz治疗：HR 0.97, 95% CI 0.77-1.21。更重要的是，通过相互作用分析观察到一个有用的预测值：含tmz治疗与单独RT治疗：(1)甲基化肿瘤：HR 0.48, 95% CI 0.36-0.65；(2)未甲基化肿瘤：HR 1.14；95% ci 0.90-1.44。结论荟萃分析报告MGMT启动子甲基化与年龄无关。更重要的是，该研究鼓励常规检测MGMT启动子状态，特别是在老年胶质母细胞瘤患者中，表明生物标志物检测与个体治疗决策之间存在直接联系。需要进一步的研究来证明在年轻患者中进行强制性检测的合理性。
Background The clinical implication of O6-methylguanine-DNA methyltransferase (MGMT) promoter status is ill-defined in elderly glioblastoma patients. Here we report a meta-analysis to seek valid evidence for its clinical relevance in this subpopulation. Methods Literature were searched and reviewed in a systematic manner using the PubMed, EMBASE and Cochrane databases. Studies investigating the association between MGMT promoter status and survival data of elderly patients (≥65 years) were eligible for inclusion. Results Totally 16 studies were identified, with 13 studies included in the final analyses. The aggregate proportion of MGMT promoter methylation in elderly patients was 47% (95% confidence interval [CI]: 42–52%), which was similar to the value for younger patients. The analyses showed differential effects of MGMT status on overall survival (OS) of elderly patients according to assigned treatments: methylated vs. unmethylated: (1) temozolomide (TMZ)-containing therapies: hazard ratio [HR] 0.49, 95% CI 0.41–0.58; (2) TMZ-free therapies: HR 0.97, 95% CI 0.77–1.21. More importantly, a useful predictive value was observed by an interaction analysis: TMZ-containing therapies vs. RT alone: (1) methylated tumors: HR 0.48, 95% CI 0.36–0.65; (2) unmethylated tumors: HR 1.14; 95% CI 0.90–1.44. Conclusion The meta-analysis reports an age-independent presence of MGMT promoter methylation. More importantly, the study encouraged routine testing of MGMT promoter status especially in elderly glioblastoma patients by indicating a direct linkage between biomarker test and individual treatment decision. Future studies are needed to justify the mandatory testing in younger patients.
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