Neil2基因rs8191670位点多态性与非小细胞肺癌化疗敏感性之间的关系

Neil2 gene rs8191670 polymorphism(T/C) is associated with chemotherapy sensitivity of non-small cell lung cancer

目的:探讨Nei核酸内切酶Ⅷ2(nei endonucleaseⅧ-like 2,Neil2)基因rs8191670位点多态性与非小细胞肺癌(non-small cell lung cancer,NSCLC)顺铂化疗敏感性之间的相关性。方法:回顾性分析2011年5月—2017年1月在郑州大学第一附属医院经病理确诊的206例晚期NSCLC患者的病理资料。应用RT-PCR法和DNA测序方法检测所有患者外周血中Neil2 mRNA 3’-非编码区基因的突变情况。Kaplan-Meier寿命表法分析患者的生存情况,log-rank检验分析Neil2基因rs8191670位点多态性(T/C)与含顺铂方案化疗敏感性及安全性的关系。结果:Neil2基因rs8191670位点存在T/C多态性。206例NSCLC患者中,Neil2基因rs8191670位点T/T纯合的为110例,T/C杂合的为54例,C/C纯合的为42例。经以顺铂为基础的二联化疗方案治疗后,T/T纯合者中位无进展生存(median progression-free survival,mPFS)时间为6.1个月,T/C杂合者为4.9个月,C/C纯合者为4.5个月,T/T纯合者的mPFS明显优于C/C纯合者(P<0.05)。不良反应分析发现,不同的基因型与患者化疗后不良反应(恶心、呕吐、腹泻,白细胞减少、贫血、血小板减少、白细胞减少相关性发热)发生率差异均无统计学意义(P值均>0.05)。结论:Neil2基因rs8191670位点多态性(T/C)通过调控Neil2蛋白的表达,改变DNA的损伤修复能力,从而对顺铂的疗效产生影响。

Objective： To reveal the association between of rs8191670 polymorphism（T/C） of Nei endonuclease Ⅷ-like 2（Neil2） gene and the sensitivity of non-small cell lung cancer（NSCLC） to cisplatin.Methods： The pathological data of 206 patients with advanced NSCLCdiagnosed in the First Affiliated Hospital of Zhengzhou University from May 2011 to January2017 were retrospectively reviewed. The mutation of 3＇-untranslated region（3＇-UTR） of Neil2 gene in peripheral blood of NSCLC patients was detected by RT-PCR and DNA sequencing.Kaplan-Meier method was used for survival analysis. The associations of the polymorphism of rs8191670 in Neil2 gene with the sensitivity and security of platinum-based chemotherapy were evaluated by the log-rank test.Results： T/C polymorphism was found in the rs8191670 locus of Neil2 gene. Among 206 NSCLC patients, there were 110 ＂T/T＂ homozygote cases, 42 ＂C/C＂ homozygote cases and 54＂T/C＂ heterozygote cases. After cisplatin-based chemotherapy, the median progression-free survival（mPFS） time of NSCLC patients bearing ＂T/T＂ homozygote in Neil2 gene rs8191670 locus was better than that of the ＂C/C＂ heterozygous patients（6.1 months vs 4.5 months,P〈 0.05）, and the mPFS of ＂T/C＂ homozygous patients was 4.9 months. There was no significant difference in the incidence of adverse reactions（including nausea, vomiting,diarrhea, leukopenia, anemia, thrombocytopenia, fever related-leukopenia） among the three genotypes of patients during chemotherapy treatment（all P 〉0.05）.Conclusion： The rs8191670 polymorphism（T/C） of Neil2 gene changes the repair ability of DNA may through regulating the expression of Neil2 protein, thus affecting the efficacy of cisplatin chemotherapy.