Department of Neurosurgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
PLoS One. 2013 Jul 22;8(7):e68782. doi: 10.1371/journal.pone.0068782. Print 2013.
Isocitrate dehydrogenase isoforms 1 and 2 (IDH1 and IDH2) mutations have received considerable attention since the discovery of their relation with human gliomas. The predictive value of IDH1 and IDH2 mutations in gliomas remains controversial. Here, we present the results of a meta-analysis of the associations between IDH mutations and both progression-free survival (PFS) and overall survival (OS) in gliomas. The interrelationship between the IDH mutations and MGMT promoter hypermethylation, EGFR amplification, codeletion of chromosomes 1p/19q and TP53 gene mutation were also revealed.
An electronic literature search of public databases (PubMed, Embase databases) was performed. In total, 10 articles, including 12 studies in English, with 2,190 total cases were included in the meta-analysis. The IDH mutations were frequent in WHO grade II and III glioma (59.5%) and secondary glioblastomas (63.4%) and were less frequent in primary glioblastomas (7.13%). Our study provides evidence that IDH mutations are tightly associated with MGMT promoter hypermethylation (P<0.001), 1p/19q codeletion (P<0.001) and TP53 gene mutation (P<0.001) but are mutually exclusive with EGFR amplification (P<0.001). This meta-analysis showed that the combined hazard ratio (HR) estimate for overall survival and progression-free survival in patients with IDH mutations was 0.33 (95% CI: 0.25-0.42) and 0.38 (95% CI: 0.21-0.68), compared with glioma patients whose tumours harboured the wild-type IDH. Subgroup analyses based on tumour grade also revealed that the presence of IDH mutations was associated with a better outcome.
Our study suggests that IDH mutations, which are closely linked to the genomic profile of gliomas, are potential prognostic biomarkers for gliomas.
自从发现异柠檬酸脱氢酶 1 和 2（IDH1 和 IDH2）突变与人类神经胶质瘤有关以来，它们受到了相当多的关注。IDH1 和 IDH2 突变在神经胶质瘤中的预测价值仍存在争议。在这里，我们对 IDH 突变与神经胶质瘤无进展生存期（PFS）和总生存期（OS）之间的相关性进行了荟萃分析。还揭示了 IDH 突变与 MGMT 启动子甲基化、EGFR 扩增、1p/19q 染色体缺失和 TP53 基因突变之间的相互关系。
对公共数据库（PubMed、Embase 数据库）进行了电子文献检索。共纳入 10 篇英文文献，包括 12 项研究，共 2190 例病例。IDH 突变在 WHO 分级 II 级和 III 级神经胶质瘤（59.5%）和继发性胶质母细胞瘤（63.4%）中较为常见，而在原发性胶质母细胞瘤（7.13%）中较为少见。我们的研究表明，IDH 突变与 MGMT 启动子甲基化（P<0.001）、1p/19q 缺失（P<0.001）和 TP53 基因突变（P<0.001）密切相关，但与 EGFR 扩增（P<0.001）相互排斥。荟萃分析显示，IDH 突变患者的总生存和无进展生存的合并危险比（HR）估计值分别为 0.33（95%CI：0.25-0.42）和 0.38（95%CI：0.21-0.68），与肿瘤携带野生型 IDH 的神经胶质瘤患者相比。基于肿瘤分级的亚组分析也表明，IDH 突变的存在与更好的预后相关。
我们的研究表明，IDH 突变与神经胶质瘤的基因组特征密切相关，是神经胶质瘤的潜在预后生物标志物。
