本文選題：晚期肺腺癌 + 培美曲塞　； 參考：《青海大學》2017年碩士論文

【摘要】：目的:探討高海拔地區(qū)晚期肺腺癌胸苷酸合成酶(thymidylate synthase,TS)和亞甲基四氫葉酸還原酶(methylene tetrahydrofolate reductase,MTHFR)基因多態(tài)性的表達及與培美曲塞聯(lián)合鉑類治療的療效觀察。方法:收集2013年9月-2016年5月的高海拔地區(qū)晚期肺腺癌患者71例,70例按要求完成隨訪。所有患者均為EGFR未突變或狀態(tài)不明者,一線接受培美曲塞聯(lián)合鉑類的方案治療。其中30例患者抽取外周血標本并提取DNA,29例按要求完成隨訪,通過聚合酶鏈反應(polymerase chain reaction,PCR)結(jié)合凝膠電泳的方法并經(jīng)測序檢測TS和MTHFR基因的多態(tài)性。分析基因多態(tài)性與臨床特征、化療療效及無進展生存期關系。結(jié)果:1.TS、MTHFR基因型分布特點:檢測29例晚期肺腺癌患者TS基因2R/2R基因型為13.8%,2R/3R的患者為34.5%,3R/3R的患者為51.7%。MTHFR基因測序結(jié)果為攜帶有C/C基因型者占34.5%,C/T基因型攜帶者為48.3%,T/T基因型攜帶者為17.2%;2.TS、MTHFR基因多態(tài)性與臨床特征的關系:TS基因多態(tài)性與年齡、性別、吸煙狀態(tài)、分期、民族、家族史等無關(P0.05)。MTHFR基因多態(tài)性分析顯示與年齡、吸煙狀態(tài)、分期、民族、家族史無關(P0.05)。MTHFR基因多態(tài)性分析顯示男性34.5%,女性65.5%,P=0.001,差異有統(tǒng)計學意義;3.TS、MTHFR基因多態(tài)性與化療療效及無進展生存期的關系:70例患者疾病控制率(disease control rate,DCR)為65.71%,中位無進展生存時間(mPFS,median progression-free survival)為9.59月;29例晚期肺腺癌患者中,TS基因3R/3R、2R/2R+2R/3R的DCR分別為60.0%和92.9%,差異有統(tǒng)計學意義(P=0.049),PFS分別為11.07月、11.29月,差異無統(tǒng)計學意義(P0.05)。MTHFR C/C和C/T+T/T基因型的DCR分別為70.0%和78.95%,PFS分別為10.00月和11.79月,差異無統(tǒng)計學意義(P0.05)。結(jié)論:高海拔地區(qū)TS基因多態(tài)性與培美曲塞治療晚期肺腺癌療效有關。MTHFR基因多態(tài)性與培美曲塞治療晚期肺腺癌療效無關。
[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.
【學位授予單位】：青海大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R734.2

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