GSTP1基因多态性与局部晚期食管癌同步放化疗疗效及预后相关性研究

目的食管癌患者在初始治疗后短期内仍然存在局部复发和远处转移的风险,影响患者预后,寻找可快速准确预测食管癌放化疗疗效和预后的生物标志物显得尤为重要。本研究通过检测外周血谷胱甘肽S转移酶P1(Glutathione S-transferase P1,GSTP1)第105位密码子Ile105Val基因多态性,探讨其与无法行手术切除的局部晚期食管鳞状细胞癌患者同步放化疗疗效及预后关系。方法选择2016-08-01-2019-02-28泰安市中心医院肿瘤内科收治的局部晚期颈段及胸中上段食管鳞状细胞癌患者为研究对象,FISH法检测外周血GSTP1 A105G基因多态性;共89例患者入组,其中突变组AG/GG者35例(39.3%),野生组AA者54例(60.7%)。入组所有患者均给予同步放化疗;按照实体瘤疗效评价标准(RECIST 2000)评价疗效,并对所有患者进行生存期的随访。选用Kaplan-Meier法和Cox比例风险回归模型进行生存分析。结果患者经同步放化疗后的疗效为CR 5例(5.6%),PR 41例(46.1%),SD 20例(22.5%),PD 23例(25.8%),总疾病控制率为74.2%;突变组疾病控制率为85.7%,高于野生组的66.7%,差异有统计学意义,χ^2=4.020,P=0.045。入组患者的1年和2年OS分别为57.3%和19.1%,中位生存期为12.4个月;突变组患者中位生存期为15.3个月,长于野生组的11.0个月,差异有统计学意义,χ^2=4.865,P=0.027。Cox多因素分析结果显示,GSTP1基因多态性是影响局部晚期食管癌患者生存的独立因素(P=0.014),GSTP1 A105G突变为局部晚期食管癌的预后保护因子(HR=0.489,95%CI为0.277~0.864)。结论 GSTP1 A105G突变组较野生组具有良好的疾病控制率及生存获益。

Correlation between GSTP1 gene polymorphism and the efficacy and prognosis of concurrent chemoradiotherapy for locally advanced esophageal carcinoma

OBJECTIVE To detect the GSTP1 Ile105Val gene polymorphismin in peripheral blood,aimed to explore its relationship with the efficacy and prognosis of concurrent chemoradiotherapy for inoperable patients with locally advanced esophageal squamous cell carcinoma.METHODS Patients with locally advanced cervical and upper thoracic esophageal squamous cell carcinoma who were treated in the Department of Oncology of Taian Central Hospital from August 1,2016 to February 28,2019 were selected as the research subjects.The polymorphism of GSTP1A105G gene in peripheral blood was detected by FISH method before treatment.A total of 89 patients were enrolled,35(39.3%)in the mutant group and 54(60.7%)in the wild group.All patients were treated with concurrent chemoradiotherapy.The curative effect was evaluated according to the solid tumor curative effect evaluation standard(RECIST 2000),and all patients were followed up for survival.Survival analysis was performed by Kaplan-Meier method and Cox proportional hazard regression model.RESULTS The effect of the patients after chemoradiotherapy were CR 5 patients(5.6%),PR 41 patients(46.1%),SD 20 patients(22.5%),PD 23 patients(25.8%),and the total disease control rate was 74.2%.Disease control rate in the mutant group was higher than that in the wild group(85.7%vs 66.7%,χ~2=4.020,P=0.045).The median survival time was 12.4 months,and the one-year and two-year overall survival were 57.3%and 19.1%,respectively.The overall survival time of mutant group was longer than that of the wild group(MST:15.3 months vs 11.0 months,χ~2=4.865,P=0.027).Cox multivariate analysis showed that GSTP1 gene polymorphisms was independent prognostic factors for overall survival(P=0.014),GSTP1A105G mutation was a protective prognostic factor in locally advanced esophageal carcinoma(HR=0.489,95%CI:0.277-0.864).CONCLUSION The mutant group of GSTP1A105G have better disease control rate and survival benefit than the wild group.