RRM1及SOD2基因多态性与晚期NSCLC铂类化疗的相关性研究  

Correlation between RRM1 and SOD2 gene polymorphisms and platinum-based chemotherapy in advanced NSCLC

作　　者：贾钦尧 宋珊[2] 王涛[2] 向小均 Jia Qinyao;Song Shan;Wang Tao;Xiang Xiaojun(School of Pharmacy,North Sichuan Medical College,Nanchong,Sichuan,637000,China;Department of Respiratory and Critical Care Medicine,Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan,637000,China;The People's hospital of Fengjie,Fengjie,Chongqing,404600,China)

机构地区：[1]川北医学院药学院,四川南充637000 [2]川北医学院附属医院呼吸与危重症科 [3]重庆市奉节县人民医院

出　　处：《西南国防医药》2021年第4期277-281,共5页Medical Journal of National Defending Forces in Southwest China

基　　金：四川省教育厅基金项目(16ZB023);川北医学院校级课题(CBY17-A-YB11)。

摘　　要：目的研究RRM1及SOD2基因多态性与晚期NSCLC铂类化疗的相关性。方法选取2017年5月~2019年10月来医院呼吸内科NSCLC铂类化疗患者252例,使用PCR扩增法分析患者的RRM1及SOD2基因多态性。采用Log-rank检验比较不同基因型的生存率,采用Cox 比例风险模型评估各影响因素对化疗效果的影响。结果 252例患者中化疗有效组(CR+PR)122 例,化疗无效组(SD+PD)130 例。TNM 分期(HR 值为 2.450)、SOD2 SNPrs4880 基因型(HR 值为 2.085)以及 RRM1RR524CT基因型(HR值为1.523)是影响化疗结局的独立危险因素(P<0.05)。RRM1 SNPrs488等位基因的C/C基因型患者的病死率明显低于其他基因型患者(T/C、T/T),SOD2 SNPrs488等位基因的C/C基因型患者的病死率明显高于其他基因型患者(T/C、T/T),差异有统计学意义(P <0.05)。RRM1及SOD2多态性间在化疗敏感性方面存在明显的相互作用,携带至少1个RRM1 RR524位点的C等位基因和SOD2 SNPrs4880位点的T等位基因的化疗有效率明显高于其他基因型携带者(P<0.05)。结论 RRM1、SOD2基因多态性可影响晚期NSCLC患者对以铂类药物为主方案的化疗疗效及生存率,二者可联合应用可预测化疗疗效,提示可根据患者基因型来指导个体化治疗。Objective To study the correlation between ribonucleotide reductase(RRM1) and superoxide dismutase(SOD2) gene polymorphisms and platinum-based chemotherapy in advanced NSCLC.Methods A total of 252 patients with NSCLC and receiving platinum-based chemotherapy in our Department of Respiratory Medicine from May 2017 to October 2019 were included.The RRM1 and SOD2 gene polymorphisms were analyzed by PCR amplification.The survival rates of different genotypes were compared by Log-rank test,and the Cox proportional hazard model was used to evaluate the influence of various influencing factors on the effect of chemotherapy.Results Among the 252 patients,122 cases were in the chemotherapy response group(CR+PR) and 130 cases were in the chemotherapy non-response group(SD+PD).TNM staging(HR value was 2.450),SOD2 SNPrs4880 genotype(HR value was 2.085),and RRM1 RR524 CT genotype(HR value was 1.523) were independent risk factors for chemotherapy outcome(P <0.05).The mortality of C/C genotype patients with RRM1 SNPrs488 allele was significantly lower than that of other genotype patients(T/C and T/T),and the mortality of C/C genotype patients with SOD2 SNPrs488 allele was significantly higher than that of other genotype patients(T/C and T/T),with statistically difference(P <0.05).There was an obvious interaction between RRM1 and SOD2 polymorphisms in chemosensitivity,and the response rate of C allele carrying at least one RRM1 RR524 locus and T allele carrying SOD2 SNPrs4880 locus was significantly higher than that of other genotype carriers(P <0.05).Conclusion RRM1 and SOD2 gene polymorphisms can affect the response and survival rate of platinum-based chemotherapy in patients with advanced NSCLC.Their combination can help predict the response of chemotherapy,suggesting that individual therapy can be guided according to the genotype of patients.

关 键 词：超氧化物歧化酶2 核糖核苷酸还原酶亚单位1 NSCLC 

分 类 号：R734.2[医药卫生—肿瘤]