Wang Luo, Wei Qingyi, Wang Li-E, Aldape Kenneth D, Cao Yumei, Okcu M Fatih, Hess Kenneth R, El-Zein Randa, Gilbert Mark R, Woo Shiao Y, Prabhu Sujit S, Fuller Greg N, Bondy Melissa L
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77230-1439, USA.
J Clin Oncol. 2006 Apr 1;24(10):1627-32. doi: 10.1200/JCO.2005.04.0402.
Glioblastoma 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 mRNA expression. We investigated whether hTERT MNS16A variant genotype predicted survival in GBM patients.
We genotyped hTERT MNS16A in 299 GBM patients using polymerase chain reaction and determined hTERT genotype 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.
Overall survival differed significantly by hTERT MNS16A genotype, with median survivals of 25.1, 14.7, and 14.6 months for the SS, SL, and LL 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.
A functional hTERT MNS16A genotype is a potential biomarker for assessment of survival outcome of GBM. Larger studies are needed to verify these findings.
多形性胶质母细胞瘤（GBM）是最常见且侵袭性最强的胶质瘤，患者生存率极低。使用生物标志物筛选GBM患者或许可用于调整治疗方案并改善预后。人端粒酶（hTERT）的表达水平是多种癌症预后的独立预测指标，并且hTERT MNS16A的一个功能变体（较短串联重复序列或短[S]等位基因）与hTERT mRNA表达增加相关。我们研究了hTERT MNS16A变体基因型是否可预测GBM患者的生存率。
我们采用聚合酶链反应对299例GBM患者的hTERT MNS16A进行基因分型，并通过将243或272碱基对（bp）的DNA条带分类为S等位基因，将302或333 bp分类为长（L）等位基因来确定hTERT基因型。我们使用Kaplan-Meier估计法比较总生存率，并使用对数秩检验比较生存分布的均等性，还计算了单变量和多变量Cox比例风险模型以估计所选变量的影响。
hTERT MNS16A基因型的总生存率存在显著差异，SS、SL和LL基因型的中位生存期分别为25.1个月、14.7个月和14.6个月。在对其他因素进行调整后，与SS基因型相比，SL和LL基因型的风险比分别为1.69和1.87。多变量Cox回归分析显示hTERT MNS16A变体基因型与预后之间存在独立的统计学显著关联。
功能性hTERT MNS16A基因型是评估GBM生存结局的潜在生物标志物。需要开展更大规模的研究来验证这些发现。
