| 苏春贺,白宏英,李 楠.高级别胶质瘤患者谷胱甘肽S-转移酶P-1多态性与替莫唑胺联合放疗疗效的相关性研究[J].中国肿瘤,2021,30(4):313-320. |
| 高级别胶质瘤患者谷胱甘肽S-转移酶P-1多态性与替莫唑胺联合放疗疗效的相关性研究 |
| Correlation Between Glutathione S-Transferase P-1 Gene Polymorphism and the Efficacy of Temozolomide Combined with Radiotherapy for Patients with High-grade Glioma |
| 中文关键词 修订日期：2020-09-01 |
| DOI：10.11735/j.issn.1004-0242.2021.04.A011 |
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| 中文关键词: 高级别胶质瘤 替莫唑胺 GSTP-1 药物基因组学 预后 |
| 英文关键词:high-grade glioma temozolomide GSTP-1 pharmacogenomics prognosis |
| 基金项目:河南省教育厅科技攻关项目（182102310517） |
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| 中文摘要: |
| 摘 要：［目的］ 探讨高级别胶质瘤患者谷胱甘肽S-转移酶P-1（glutathione S-transferase P-1，GSTP-1）基因多态性与替莫唑胺联合放疗疗效的相关性。［方法］ 本研究从2012年1月至2019年12月纳入268例术后接受替莫唑胺联合放疗辅助治疗的高级别胶质瘤患者。通过病例系统获取患者的基线临床资料，以及后期的电话随访获取患者的预后数据，进而分析替莫唑胺联合放疗方案的预后。在患者住院期间收集患者外周血样本进行GSTP-1多态性的基因分型，并结合基线临床资料进行相应的关联分析。此外，收集可用于mRNA表达分析的样本进行GSTP-1基因的表达分析，进而探讨该位点对GSTP-1基因mRNA表达的影响。［结果］ 268例患者的中位无进展生存期为7.0个月，中位总生存期为13.5个月。关联分析中只发现了位于GSTP-1基因编码区域的313A>G位点和预后显著相关。313A>G位点在研究人群中的分布频率为：AA型182例（67.9%），AG型79例（29.5%），GG型7例（2.6%），最小等位基因频率为0.17，该位点基因型分布频率符合哈迪温伯格平衡（P=0.649）。AA基因型和AG/GG基因型患者的中位无进展生存期分别为9.0个月和5.8个月，差异具有显著的统计学意义（χ2=14.51，P<0.001）。总生存期方面，AA型和AG/GG基因型患者的中位总生存期分别为15.5个月和10.0个月，差异具有显著的统计学意义（χ2=9.53，P=0.002）。多因素分析中，针对PFS构建的Cox模型结果表明AG/GG基因型对PFS具有独立的影响（HR=1.56，P=0.005）。mRNA分析结果表明在88例外周血单核细胞标本的mRNA表达分析中，313A>G位点AG/GG基因型患者相对于野生型的AA基因型患者，PBMC标本中GSTP-1的mRNA表达显著较高（P<0.001）。［结论］ 高级别胶质瘤患者接受替莫唑胺联合放疗的辅助治疗具有和既往研究类似的预后，GSTP-1基因313A>G多态性位点可能成为评估该方案预后的药物基因组因素。 |
| 英文摘要: |
| Abstract：［Purpose］ To investigate the correlation between Glutathione S-Transferase P-1(GSTP-1) gene polymorphism and the efficacy of temozolomide combined with radiotherapy for patients with high-grade glioma. ［Methods］ A total of 268 patients with high-grade glioma who receiving temozolomide combined with radiotherapy after surgical resection from January 2012 to December 2019 were enrolled in this study. Baseline clinical characteristics were obtained through electronic medical records system and outcomes of patients were obtained by telephone follow-up. Peripheral blood of patients was collected for genotyping of GSTP-1 gene polymorphism. The mRNA expression of GSTP-1 gene was detected with RT-PCR. The correlation of GSTP-1 polymorphism with therapeutic efficacy was analyzed. ［Results］ The median progression free survival(mPFS) of the 268 patients was 7.0 months，the median overall survival(mOS) was 13.5 months. The 313A>G of GSTP-1 gene coding region was correlated with the prognosis of patients. The distribution of 313A>G genotypes：AA genotype in 182 cases(67.9%)，AG genotype in 79 cases(29.5%)，GG genotype in 7 cases(2.6%)，and the minor allele frequency of 313A>Gis was 0.17. The distribution of three genotypes were in accordance with Hardy-Weinberg Equilibrium(P=0.649). The prognosis analysis indicated that the mPFS of patients with AA and AG/GG genotypes was 9.0 and 5.8 months，respectively(χ2=14.51，P<0.001)；the mOS of the two genotypes was 15.5 and 10.0 months，respectively(χ2=9.53，P=0.002). Multivariate Cox regression analysis showed that AG/GG genotype was an independent factor for PFS(HR=1.56，P=0.005). The expression of GSTP-1 mRNA in PBMC of the patients with AG/GG genotypes was significantly higher than that of the AA genotype(P<0.001). ［Conclusion］ Patients with high-grade glioma receiving temozolomide combined with radiotherapy demonstrate a similar prognosis to previous studies.The 313A>G polymorphism of GSTP-1 might be a pharmacogenomic factor in evaluating the prognosis of the regimen. |
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