Survival prediction in patients with glioblastoma multiforme by human telomerase genetic variation
Survival prediction in patients with glioblastoma multiforme by human telomerase genetic variation
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DOI：
10.1200/jco.2005.04.0402
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发表时间：
2006-04-01
影响因子：
45.3
通讯作者：
Bondy, ML
中科院分区：
文献类型：
--
作者：
Wang, L;Wei, QY;Bondy, ML
多形性胶质母细胞瘤（GBM）是最常见、最具侵袭性、生存率最低的胶质瘤。使用生物标志物筛查GBM患者可用于修改治疗和改善结局。人端粒酶（hTERT）表达水平是许多癌症预后的独立预测因素，hTERT MNS 16 A的功能变体（较短串联重复序列或短[S]等位基因）与hTERT表达增加相关。我们调查是否hTERTMNS 16 A变异基因型预测生存GBM patients.Patients和MethodsWe基因型hTERTMNS 16 A在299 1例患者使用聚合酶链反应和确定hTERTgenotype通过分类的DNA带243或272碱基对（bp）的S等位基因和302或333 bp的长（L）等位基因。我们使用Kaplan-Meier估计和平等的生存分布，使用对数秩检验，我们计算单变量和多变量的考克斯比例风险模型，以估计选定的variables.ResultsOverall survival different显着hTERT MNS 16 A基因型，与中位生存期为25.1，14.7，和14.6个月的SS，SL和ILL基因型，分别。与SS基因型相比，校正其他因素后，SL和LL基因型的风险比分别为1.69和1.87。多因素考克斯回归分析显示hTERTMNS 16 A变异基因型与GBM预后之间存在独立的统计学显著性关联。需要更大规模的研究来验证这些发现。
PurposeGlioblastoma multiforme (GBM) is the most common and aggressive glioma with the poorest survival. Use of biomarkers for screening patients with GBM may be used to modify treatments and improve outcomes. The level of human telomerase (hTERT) expression is an independent predictor of outcome of many cancers, and a functional variant of hTERT MNS16A (shorter tandem repeats or short [S] allele) is associated with increased hTERT expression. We investigated whether hTERT MNS16A variant genotype predicted survival in GBM patients.Patients and MethodsWe genotyped hTERT MNS16A in 299 1 patients using polymerase chain reaction and determined hTERTgenotype by classifying the DNA band of 243 or 272 base pairs (bp) as S allele and 302 or 333 bp as long (L) allele. We compared overall survival using Kaplan-Meier estimates and equality of survival distributions using the log-rank test, and we computed univariate and multivariate Cox proportional hazards models to estimate the effects of selected variables.ResultsOverall survival differed significantly by hTERT MNS16A genotype, with median survivals of 25.1, 14.7, and 14.6 months for the SS, SL, and ILL genotypes, respectively. Compared with the SS genotype, the hazard ratios for the SL and LL genotypes were 1.69 and 1.87, respectively, after adjustment for other factors. Multivariate Cox regression analysis showed an independent statistically significant association between the hTERT MNS16A variant genotype and outcome.ConclusionA functional hTERT MNS16A genotype is a potential biomarker for assessment of survival outcome of GBM. Larger studies are needed to verify these findings.