lncRNA HOTAIR基因多态性与铂类联合化疗对晚期非小细胞肺癌患者的疗效及毒性反应的相关性研究  

Correlation of lncRNA HOTAIR Gene Polymorphisms with the Efficacy and Toxicity of Platinum-Based Chemotherapy in Patients with Advanced NSCLC

作　　者：姜科 刘晋湘 陈宇 汪国庆 刘小兰 李波[1] JIANG Ke;LIU Jinxiang;CHEN Yu;WANG Guoqing;LIU Xiaolan;LI Bo(The Fourth Department of Oncology,Sichuan Friendship Hospital,Chengdu,Sichuan,610500,China)

机构地区：[1]四川省人民医院友谊医院肿瘤四科,四川成都610500

出　　处：《肿瘤药学》2020年第4期483-489,共7页Anti-Tumor Pharmacy

摘　　要：目的探究lncRNA HOTAIR基因多态性与铂类联合化疗对晚期非小细胞肺癌(NSCLC)患者疗效及毒副反应的相关性。方法选择2014年1月—2018年1月在我院确诊并接受治疗的280例晚期NSCLC患者作为研究对象,采用铂类药物联合化疗,2个周期后评价临床疗效和毒副反应。采用改进多重高温连接酶检测反应(iMLDR)进行rs12826786(C>T)、rs4759314(A>G)、rs920778(C>T)、rs1899663(G>T)基因分型。采用SPSS 23.0软件计算比值比(OR)及95%置信区间(CI),评估lncRNA HOTAIR位点变异与铂类联合化疗疗效及毒副反应的相关性。结果rs12826786和rs4759314的显性模型与较高的化疗有效率相关(rs12826786:OR=3.036,95%CI=1.153~8.041;rs4759314:OR=2.895,95%CI=1.213~7.646);rs920778和rs1899663的隐性模型与较高的化疗有效率有关(rs920778:OR=3.057,95%CI=1.382~8.669;rs1899663:OR=3.154,95%CI=1.256~10.649)。rs12826786和rs920778位点多态性与铂类联合化疗的血液学毒性反应有关,rs12826786的CT+TT基因型较野生型CC更易出现严重血液学毒性(OR=0.559,95%CI=0.147~0.832),而rs920778的CT+TT基因型严重血液学毒性的发生率低于CC型(OR=2.545,95%CI=1.349~5.337)。HOTAIR的rs920778位点多态性与胃肠道毒性反应有关,携带突变等位基因T的患者更易发生0-Ⅱ级胃肠道毒性反应(OR=3.558,95%CI=1.607~8.695)。结论lncRNA HOTAIR基因多态性与晚期NSCLC患者铂类联合化疗的疗效及毒副反应相关,有一定的临床预测价值。Objective To explore the correlations of lncRNA HOX transcript antisense RNA(HOTAIR)gene polymorphism with the efficacy and toxicity of platinum-based chemotherapy in patients with advanced non-small cell lung cancer(NSCLC).Methods Two hundred and eighty cases of advanced NSCLC patients diagnosed and treated in our hospital between January 2014 and January 2018 were selected as the research objects.They all got platinum-based chemotherapy.The clinical efficacy and side effects were evaluated after two cycles.The genotypes of rs12826786(C>T),rs4759314(A>G),rs920778(C>T)and rs1899663(G>T)were determined by improved multiplex ligase detection reaction(iMLDR)method.The odds ratio(OR)and 95%confidence interval(CI)were calculated by SPSS 23.0 software to evaluate the correlation between lncRNA HOTAIR gene variations and the efficacy and toxicity of platinum-based chemotherapy.Results The dominant models of rs12826786 and rs4759314 were correlated with higher chemotherapy response rate(rs12826786:OR=3.036,95%CI=1.153~8.041);rs4759314:OR=2.895,95%CI=1.213~7.646 .While the recessive models of rs920778 and rs1899663 were correlated with higher chemotherapy response rate(rs920778:OR=3.057,95%CI=1.382~8.669;rs1899663:OR=3.154,95%CI=1.256~10.649).There was a relationship between the rs12826786 and rs920778 polymorphisms and the hematological toxicity of platinum-combined chemotherapy.The CT+TT genotype of rs12826786 was more prone to severe hematological toxicity than wild-type CC(OR=0.559,95%CI=0.147~0.832),while the incidence of severe hematological toxicity in CT+TT carriers of rs920778 was lower than that of CC carriers(OR=2.545,95%CI=1.349~5.337).The polymorphism of rs920778 locus of HOTAIR was related to gastrointestinal toxicity,and patients with mutant allele T were more likely to have grade 0-Ⅱgastrointestinal toxicity(OR=3.558,95%CI=1.607~8.695).Conclusion lncRNA HOTAIR gene polymorphism was related to the efficacy and toxicity of platinum-based chemotherapy in patients with advanced NSCLC,so it had certain clinic

关 键 词：长链非编码RNA HOX转录反义RNA 非小细胞肺癌 铂类药物 化疗毒性 

分 类 号：R734.2[医药卫生—肿瘤]