【摘要】 目的:替莫唑胺联合放疗在新诊断脑胶质瘤的辅助治疗中具有重要治疗地位,谷胱甘肽S-转移酶P-1(Glutathione S-Transferase P-1,GSTP1)在胶质瘤细胞外源性物质解毒过程中具有重要作用,可能影响替莫唑胺联合放疗对肿瘤细胞的杀伤力。本研究旨在探讨GSTP1基因遗传变异对接受替莫唑胺联合放疗的脑胶质瘤患者预后的影响。方法:本研究纳入175例手术切除后接受替莫唑胺联合放疗辅助治疗的脑胶质瘤患者。收集患者外周血进行GSTP1基因多态性位点基因分型。多态性位点的基因型和其他变量的相关性通过卡方检验或非参检验方法进行分析。收集部分患者接受放化疗前的新鲜外周血单核细胞(peripheral blood mononuclear cell,PBMC)标本提取RNA定量分析GSTP1 mRNA表达。并分析基因型和预后的关联。结果:Ile105Val变异在研究人群中的突变频率为:AA型119例(68. 00%),AG型51例(29. 14%),GG型5例(2. 86%),最小等位基因频率为0. 17,该位点基因型分布频率符合Hardy-Weinberg平衡(P=0. 868)。随后以显性遗传方式将AG型和GG型患者合并进行分析。预后分析结果表明:AG/GG基因型和AA基因型患者的中位无进展生存期分别为4. 4和6. 9个月,差异有统计学意义(P=0. 005)。在总生存期(overall survival,OS)方面,AG/GG型和AA基因型患者的中位OS分别为11. 0和15. 3个月,差异有统计学意义(P <0. 001)。针对OS的多变量的Cox分析结果表明,AG/GG基因型对OS具有独立的影响意义(OR=1. 68,P=0. 011)。78例PBMC标本的GSTP1基因mRNA表达实验结果表明,Ile105Val变异AG/GG基因型患者GSTP1的mRNA表达水平显著高于AA基因型患者[(4. 01±0. 472) vs (2. 76±0. 624),P <0. 001]。结论:GSTP1基因Ile105Val变异是影响接受替莫唑胺联合放疗辅助治疗的胶质瘤患者预后的生物标志物。更多还原

【Abstract】 Objective: The regimen of temozolomide plus radiotherapy plays an important role in the adjuvant therapy of newly diagnosed glioblastoma. Glutathione S-transferase P-1( GSTP1) is of great value in detoxification of xenobiotics in glioblastoma cells. Therefore,it plays a certain role in the killing of cancer cells by temozolomide,an antitumor drug,and radiation. This study was designed to investigate the influence of genetic variation in GSTP1 on the prognosis of glioblastoma patients received temozolomide combined with radiotherapy. Methods: A total of 175 patients with glioblastoma treated with temozolomide combined with radiotherapy after surgery were included in this study. Peripheral blood of patients was collected for the genotyping of genetic polymorphisms in GSTP1 gene. The correlation between genotype and other variables was analyzed by Chi-square test or nonparametric test. RNA was extracted from peripheral blood mononuclear cell( PBMC) specimens of some patients prior to chemotherapy for GSTP1 mRNA expression analysis. Association between genotype and prognosis was analyzed. Results: The mutation frequency of the GSTP1 Ile105 Val variant in the study population was 68. 00%( 119 cases) in genotype AA,29. 14%( 51 cases) in genotype AG,and 2. 86%( 5 cases) in genotype GG. The minimum allele frequency was 0. 17. The frequency of genotype distribution in this site was in accordance with Hardy-Weinberg equilibrium( P = 0. 868). Type AG patients and type GG patients were then analyzed with dominant inheritance. The median progression-free survival of type AG/GG patients and type AA patients were 4. 4 and 6. 9 months( P = 0. 005),respectively.The median overall survival of the two genotypes was 11. 0 and 15. 3 months( P < 0. 001),respectively. Multivariate Cox regression analysis showed that genotype AG/GG was an independent factor for OS( OR = 1. 68,P = 0. 011). Of the 78 PBMC specimens,the mRNA expression of GSTP1 in PBMC of genotype AG/GG patients in was significantly higher than that of genotype AA patients( 4. 01 ± 0. 472 vs 2. 76 ± 0. 624,P < 0. 001). Conclusion: GSTP1 gene( Ile105 Val) polymorphism was a biomarker for prognosis of glioblastoma patients received temozolomide combined with radiotherapy.更多还原