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在调整胶质母细胞瘤患者的RPA分级后,H-MLH1的预后价值。

Prognostic value of H-MLH1 after adjusting for RPA class in GBM patients.

作者信息

Choucair Ali, Moughan Jennifer, Schultz Chris, Schulsinger Alan, Mehta Minesh, Curran Walter

机构信息

Intermountain Medical Center, Neuroscience Center, Murray, Utah 84107, USA.

出版信息

Front Biosci (Elite Ed). 2011 Jun 1;3(3):1182-91. doi: 10.2741/e321.

Abstract

Repair of DNA adducts appears to be an important mechanism in chemotherapy responsiveness in glioblastoma multiforme (GBM). Meta-analyses have suggested that the addition of chemotherapy increases the percentage of long-term survivors. Because GBM is characterized by multiplicity of pathways that characterize growth and treatment resistance, we hypothesized probing a multiplicity of repair factors may be able to identify more than one prognostic factor that may be utilized in molecularly targeted therapy that might improve survival and QOL. Seven DNA repair factors showed statistical significance when added to the initial logistic model of RPA class on length of survival status. After adjusting for RPA class the only statistically significant result of the multivariable logistic regressions for these 7 DNA repair factors was that as hMLH1-MF1 increased, the odds of being a short-term survivor versus a long-term survivor decreased (OR: 0.913, 95 per cent CI: 0.838-0.995, p=0.0385), multivariable analysis showed no associations between survival status and MGMT and p53 status, and the only statistically significant prognostic DNA repair factor was human Mut L Homologue 1 (hMLH1).

摘要

DNA加合物的修复似乎是多形性胶质母细胞瘤(GBM)化疗反应性的一种重要机制。荟萃分析表明,添加化疗可提高长期存活者的比例。由于GBM的特征是具有多种与生长和治疗抗性相关的途径,我们推测探究多种修复因子或许能够识别出不止一种可用于分子靶向治疗的预后因子,从而可能改善生存和生活质量。当将七种DNA修复因子添加到关于生存状态时长的RPA分类的初始逻辑模型中时,显示出统计学意义。在对RPA分类进行调整后,这七种DNA修复因子的多变量逻辑回归中唯一具有统计学意义的结果是,随着hMLH1-MF1增加,短期存活者与长期存活者相比的几率降低(比值比:0.913,95%置信区间:0.838 - 0.995,p = 0.0385),多变量分析显示生存状态与MGMT和p53状态之间无关联,唯一具有统计学意义的预后DNA修复因子是人类Mut L同源物1(hMLH1)。

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