高海拔地区晚期肺腺癌TS,MTHFR基因多态性与培美曲塞治疗临床研究

发布时间：2018-06-30 20:13

本文选题：晚期肺腺癌 + 培美曲塞　；参考：《青海大学》2017年硕士论文

【摘要】：目的:探讨高海拔地区晚期肺腺癌胸苷酸合成酶(thymidylate synthase,TS)和亚甲基四氢叶酸还原酶(methylene tetrahydrofolate reductase,MTHFR)基因多态性的表达及与培美曲塞联合铂类治疗的疗效观察。方法:收集2013年9月-2016年5月的高海拔地区晚期肺腺癌患者71例,70例按要求完成随访。所有患者均为EGFR未突变或状态不明者,一线接受培美曲塞联合铂类的方案治疗。其中30例患者抽取外周血标本并提取DNA,29例按要求完成随访,通过聚合酶链反应(polymerase chain reaction,PCR)结合凝胶电泳的方法并经测序检测TS和MTHFR基因的多态性。分析基因多态性与临床特征、化疗疗效及无进展生存期关系。结果:1.TS、MTHFR基因型分布特点:检测29例晚期肺腺癌患者TS基因2R/2R基因型为13.8%,2R/3R的患者为34.5%,3R/3R的患者为51.7%。MTHFR基因测序结果为携带有C/C基因型者占34.5%,C/T基因型携带者为48.3%,T/T基因型携带者为17.2%;2.TS、MTHFR基因多态性与临床特征的关系:TS基因多态性与年龄、性别、吸烟状态、分期、民族、家族史等无关(P0.05)。MTHFR基因多态性分析显示与年龄、吸烟状态、分期、民族、家族史无关(P0.05)。MTHFR基因多态性分析显示男性34.5%,女性65.5%,P=0.001,差异有统计学意义;3.TS、MTHFR基因多态性与化疗疗效及无进展生存期的关系:70例患者疾病控制率(disease control rate,DCR)为65.71%,中位无进展生存时间(mPFS,median progression-free survival)为9.59月;29例晚期肺腺癌患者中,TS基因3R/3R、2R/2R+2R/3R的DCR分别为60.0%和92.9%,差异有统计学意义(P=0.049),PFS分别为11.07月、11.29月,差异无统计学意义(P0.05)。MTHFR C/C和C/T+T/T基因型的DCR分别为70.0%和78.95%,PFS分别为10.00月和11.79月,差异无统计学意义(P0.05)。结论:高海拔地区TS基因多态性与培美曲塞治疗晚期肺腺癌疗效有关。MTHFR基因多态性与培美曲塞治疗晚期肺腺癌疗效无关。
[Abstract]:Objective: to investigate the expression of thymidylate synthase (TS) and methylene tetrahydrofolate reductase (methylene tetrahydrofolate MTHFR) gene polymorphism in advanced lung adenocarcinoma at high altitude. Methods: 71 patients with advanced lung adenocarcinoma from September 2013 to May 2016 were followed up as required. All patients were EGFR unmutated or unknown, and were treated with pemetrexide combined with platinum regimen. Among them, 30 patients were collected from peripheral blood and 29 patients were followed up according to request. The polymorphisms of TS and MTHFR genes were detected by polymerase chain reaction (polymerase chain) reaction- PCR combined with gel electrophoresis and sequencing. To analyze the relationship between gene polymorphism and clinical features, chemotherapeutic efficacy and progression-free survival. Results: 1. The distribution of MTHFR genotypes: 29 patients with advanced lung adenocarcinoma were detected TS gene 2R / 2R genotype was 13.8R / 3R and 34.5% 3R / 3R patients were 34.7%. MTHFR gene sequencing results showed that 34.5% C / C genotype carriers were 38.3C% T / T genotype carriers were 48.3C% T / T genotype carriers were 38.3C / 3R / 3R / 3R / 3R / 3R / 3R / 3R / 3R / 3R / 3R / 3R / 3R / 3R / 3R / 3R / 3R / 3R patients respectively The relationship between the polymorphism of TSN MTHFR gene and clinical features was 17.2% TS gene polymorphism and age. Gender, smoking status, stage, nationality, family history, etc. (P0.05) .MTHFR gene polymorphism analysis showed that it was associated with age, smoking status, stage, nationality, etc. Family history was not significant (P0.05) .MTHFR gene polymorphism analysis showed that 34.5% male and 65.5% female patients had significant difference. The relationship between MTHFR gene polymorphism and chemotherapeutic efficacy and progression-free survival time was 65.71in 70 patients with (disease control rateor, with median no progression. In 29 patients with advanced lung adenocarcinoma with median progression-free survival of 9.59 months, the DCRs of TS gene 3R / 3R / 2R 2R / 3R were 60.0% and 92.9%, respectively. The difference was statistically significant (P0.049). The DCR of MTHFR C / C and C / T T / T genotypes were 70.0% and 78.95%, respectively (P 0.05). There was no significant difference in DCR between MTHFR C / C and C / T T / T genotypes (P 0.05). Conclusion: the polymorphism of TS gene in high altitude area is related to the efficacy of pemetrexed in the treatment of advanced lung adenocarcinoma. The polymorphism of MTHFR gene is not related to the efficacy of pemetrexed in the treatment of advanced lung adenocarcinoma.
【学位授予单位】：青海大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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