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谷胱甘肽S-转移酶P-1(GSTP-1)基因多态性对接受替莫唑胺联合放疗辅助治疗的高级别胶质瘤患者预后的影响

Influence of GSTP-1 Polymorphism on the Prognosis of Patients with High-Grade Glioma Who Received Temozolomide Plus Radiotherapy Adjuvant Treatment.

作者信息

Zhi De-Bao, Wang Zhi-Yu, Xie Tong, Tu Wen-Wen

机构信息

Department of Surgical Care Unit, Xuhui District Central Hospital, Shanghai, 200031, People's Republic of China.

Department of Neurosurgery, Xuhui District Central Hospital, Shanghai, 200031, People's Republic of China.

出版信息

Int J Gen Med. 2021 Dec 22;14:10173-10183. doi: 10.2147/IJGM.S328810. eCollection 2021.

Abstract

BACKGROUND

Glutathione S-Transferase P 1 (GSTP-1) gene plays an important physiological role in the body. The present study was conducted to identify the clinical implication of GSTP-1 gene polymorphism on the prognosis of patients with high-grade glioma (HGG) who received temozolomide plus radiotherapy adjuvant treatment.

METHODS

This study recruited a total of 186 patients with HGG who were treated with temozolomide plus radiotherapy adjuvant regimen (retrospectively). Baseline clinical characteristics were obtained and the prognostic data of the patients were collected. Peripheral blood specimen of patients was preserved for genotyping of GSTP-1 polymorphism during hospitalization. Correlation analysis was carried out accordingly. Additionally, fresh peripheral blood specimens that were available for mRNA expression analysis were collected for the mRNA expression analysis.

RESULTS

The median progression-free survival (PFS) and overall survival (OS) of the 186 patients with HGG who received temozolomide plus radiotherapy regimen was 8.5 months (95% CI: 5.95-11.05) and 15.5 months (95% CI: 11.49-19.51), respectively. The prevalence of 313A>G among 186 patients with glioma was AA genotype: 126 cases (67.7%), AG genotype: 54 cases (29.1%), GG genotype: 6 cases (3.2%), minor allele frequency of 313A>G was 0.18. Association analysis suggested that the median PFS of patients with AA and AG/GG genotypes was 11.2 and 5.0 months, respectively (χ=11.17, =0.001). Furthermore, the median OS of patients with AA and AG/GG genotypes was 18.9 and 10.5 months, respectively (χ=12.684, <0.001). Besides, when adjusted for PFS in multivariate Cox regression analysis, AG/GG genotype was an independent factor for PFS (HR=0.48, =0.006). The mRNA expression results indicated that mRNA expression of GSTP-1 in patients with AG/GG genotypes of 313A>G was significantly higher than that of patients with AA genotype (<0.001).

CONCLUSION

GSTP-1 polymorphism 313A>G might be used as a potential biomarker to predict the prognosis of patients with HGG who received temozolomide plus radiotherapy adjuvant treatment.

摘要

背景

谷胱甘肽S-转移酶P1(GSTP-1)基因在体内发挥重要的生理作用。本研究旨在确定GSTP-1基因多态性对接受替莫唑胺联合放疗辅助治疗的高级别胶质瘤(HGG)患者预后的临床意义。

方法

本研究共纳入186例接受替莫唑胺联合放疗辅助方案治疗的HGG患者(回顾性研究)。获取患者的基线临床特征并收集其预后数据。患者住院期间采集外周血标本用于GSTP-1基因多态性基因分型。相应地进行相关性分析。此外,收集可用于mRNA表达分析的新鲜外周血标本进行mRNA表达分析。

结果

186例接受替莫唑胺联合放疗方案的HGG患者的中位无进展生存期(PFS)和总生存期(OS)分别为8.5个月(95%CI:5.95 - 11.05)和15.5个月(95%CI:11.49 - 19.51)。186例胶质瘤患者中313A>G的基因型分布为:AA基因型126例(67.7%),AG基因型54例(29.1%),GG基因型6例(3.2%),313A>G的次要等位基因频率为0.18。关联分析表明,AA基因型和AG/GG基因型患者的中位PFS分别为11.2个月和5.0个月(χ = 11.17,P = 0.001)。此外,AA基因型和AG/GG基因型患者的中位OS分别为18.9个月和10.5个月(χ = 12.684,P < 0.001)。此外,在多因素Cox回归分析中对PFS进行校正后,AG/GG基因型是PFS的独立影响因素(HR = 0.48,P = 0.006)。mRNA表达结果表明,313A>G的AG/GG基因型患者的GSTP-1 mRNA表达显著高于AA基因型患者(P < 0.001)。

结论

GSTP-1基因多态性313A>G可能作为预测接受替莫唑胺联合放疗辅助治疗的HGG患者预后的潜在生物标志物。

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